I've been experiencing some strange issues lately.  I very often use the jogging in Mach4.  Lately if will just stop working.  Yesterday I was running some G code and hit stop.  Then tried to jog for some manual drilling and the jogging stopped working however I could still using button jog.  All other buttons were not selectable.  I ended up having to close and re-open Mach 4.  I've had a number of these issues that force me to close and re-open.  Even had a crash a few days ago that I started a jog and let up and it just kept going. Only thing that stopped it was the E-button!  Running 4.2.0.3481.

Thanks for any help.  Also running PMDX-424 that does not have to be reset.

Maybe try updating Mach and your motion plugin?  3481 is ancient.  4300 is on the website here: https://www.machsupport.com/downloads-updates/main-programs/

Please backup your current installation before updating. 

Steve