2003 f-250 2wd,5.4L, with trans harness unplugged at trans runs fine.
Could use a little more info -- like what engine speed and load the misfire is occurring.
That fact that unplugging the transmission electrical connector makes a difference could mean a couple of things.
One, the misfire may only be felt under light load at highway speeds with the Lockup torque converter engaged (won't engage with the trans unplugged). Two, it may not be a true misfire, but a problem with poor torque converter engagement (judder).
First thing to do is check for trouble codes. Misfire DTCs would confirm the problem is in the engine, not the transmission.
Get us some more details so we can take it a little further.
maybe misfire is wrong word, how bout seems to short out coils or injectors, stall speed load just off idle, wont rev up in gear, all codes trans related, no engine codes, will rev up in park, thanks, Roscoe
OK, "all codes trans related" is the place to start.
Let us know the codes, and we can help you with some potential causes.
Subscribe to ALLDATAdiy.com, and try to diagnose the codes yourself.
Or get the truck to a repair shop (preferably a Ford service department), and get an accurate diagnosis that way (about $100).