can you try with MOUSE.COM instead of mouse.sys? mouse.com gets loaded from autoexec
also when you get it working bMOUSE is great for duke3d: http://swisscm.duke4.net/ it will make mouse usage better

Ok, so i just installed mouse.com to c:\, edited config.sys and REM, then autoexec.bat, LH c:\mouse.com and saved then rebooted... the mouse is found in POST ... but now when I launch Duke Nukem 3D... it crashes at the Loading screen... 🤣

If the game locks up (or used to lock up) when you move the mouse, there's a chance that your system has an IRQ conflict. Or perhaps the mouse driver you're using is incompatible with the DOS/4GW extender used by the game.

To get started, check if the mouse works correctly in DOS programs like EDIT or QBASIC and report the results here.

Also, it might help if you can tell what kind of mouse you're using (COM or PS/2, manufacturer, etc.) and what mouse driver you're trying to use. I don't remember MS-DOS 6.22 shipping with a built-in mouse driver. And you can't just take any old DOS mouse driver and expect it to work with a mouse that it wasn't designed for. If your mouse driver can't handle your mouse correctly, then that might also be the reason why your system locks up.

Just a shot in the dark but is this a PS/2 mouse? I believe those tend to use IRQ12 and can potentially conflict with any network cards that may use IRQ12. Does the machine have a network card? Any other add on cards besides VGA and sound ?

Crashing the moment an interrupt is generated is pointing towards a conflict IMO. Dig around in the bios for any IRQ options and run MSD (Microsoft Diagnostic) and see if you can find anything unusual. If you find nothing do as was said above and see if this crashing occurs in any other software using the mouse, or if it can just be narrowed down to Duke3d.

Sorry, I have been trying to install a new sound card... going nuts with CTCM.... anyhow, got the CT3620 working but with a duff ram moduale... Why? 'cause I thought that it was the Sound Blaster Vibra giving me grief... but no! So, I have read your posts (Thank you) and to answer the questions:
I have / am using a standard PS/2 mouse (Microsoft 2.0A)... connected to the PS/2 port of the motherboard.
The mouse drivers work fine, as in, I have copied MOUSE.SYS to c:\ and into config.sys. Device=C:\mouse.sys...
I can use the mouse in c:\sb16\diagnose... 'cause I just did to test that damn 32PNP! and also in MSD.... 🤣
When I launch duke Nukem 3D... it states MOUSE PRESENT... so that must be good?
and finally, I am just stareing at MSD... IRQ 12... (reserved).... PS/2 style mouse.... handled by AGMS...
which brings me to the final question ... no, no NIC installed just the SB32awePNP and S3TRio64+ ..... onboard VGA disabled in bios... Voila c'est tout..!

so, now that i'm loking for IRQ conflicts... i'll look for a conflict....

And because, I was interested, I just plugged in a Microsoft serial mouse 2.0a on COM1... booted...the mouse was found on com 1... worked in MSD... and believe it or believe it not... it too crashes the game as soon as I move the mouse...just wanted to share that with you... and while i'm doing that, i'll also point out (no pun) that I use the same mouse drivers and the same mouse on a 486DX2 66 set up running MS-DOS 6.22, and it works very well with Duke... so i guess its down to the IBM hardware / software...

Whilst I've been trying out a few things, i'd just like to say that the mouse does not work in Syndicate nor DOOM.... and i'm also not getting any music in DOOM... so I am at a total loss now... i'll see if I can find another mouse driver of the web...

In the future, ask old hardware and driver/configuration questions in Marvin. This forum is for old Windows games on *modern* systems. Marvin, the Paranoid Android

try duke3d with no sound and no music configured in setup to rule out soundcard conflicts

Those alien bastards are gonna pay for shooting up my ride and hey presto the mouse works...! I wish to thank everyone who posted and with all the elements, I have now got a working mouse... How did I solve the problem? we'll I (as in ME) didn't but here is the break down and at the end the name of the winner.

So, I messed around trying to un-bind IRQ 12 in the bios... yep, it says you can, so I did.... but when DOS had booted and I checked MSD... The damn mouse was still assigned to IRQ 12.

Then I spent a few hours reading different websites about the IBM PS/2 mouse controller... and fell asleep....

Had another shot removing the mouse and re-installing the driver from the Original mouse driver disk from Microsoft... well, the Dsetup.ini file got lost between the floppy and the floppy drive... so that didn't work...

Then, and this is the best part, I put back the original drivers I had installed, and followed... the advice about checking the game with out sound... The game still crashed but this time Duke was just spinning around on himself...so, hmmm.... kind of like onto something here... but still had to hard reset...

Ok, so I know that IBM used Logitech mice as OEM stuff.... so, I swapped the MicroSoft mouse over for a Logitec one.... and the game still crashed...but Duke was happy just standing there rubbing his hands....

Ok, get on with it, what did you do?

Well, I did a edit c:\mouse.sys and felt that the gibberish could be the reason for the problem... saying that I could make out the / options.. like /B... so, I treid that...and nope no bus mouse found...

Finally, I had another look in my FDD box and found a copy of MOUSE.SYS and MOUSE.COM drivers... I felt this was just a back-up and thought what the heck... I xcopyied over the file and rebooted... and it rebooted as MICROSOFT MOUSE DRIVER 6.10.... (very important !!!)

relaunched Duke without sound and held my breath when I touched the mouse... and Duke moved ... and then moved some more... he moved left, he moved right....

Right, so that seems to have solved the problem.. back to sound set up and sound card choice.... OK

Game relaunch and Duke is now racing around on all two legs being controlled by a logitech mouse with microsoft mouse drivers.... Oh the Irony!!!

THANK YOU GUYS FOR ALL YOUR HELP and sorry for posting in the wrong place... I was sure this stuff was modern... 😊 😎

^ great you got it solved!
do try bmouse I posted about, really works wonders with build games.