I have a 90' SuperDuty SWB 2WD 460 EFI. The problem I'm having is it either will shut completely off or will start to run rough and only idle till eventually shut down, after driving 5-10 miles. It will only start if I tamper with fuel system (remove filter, bleed off relief valve, etc.) ok, what I've done recently is change complete distributor due to being worn out, I've installed new fuel tank, pump, due to rusted out tank. Ran great for probably 500 miles then this problem started as I've mentioned above, I have great pressure at relief valve on fuel rail, so I replaced fuel regulator and it will run good for 5-10 mile then problem starts again. Now I don't use far rear tank due to previous owner said he never used so I was gonna replace rear tank and pump before I even tried it! Can't figure this front tank issue out. Thanks for any help.

 

Have you tried running it with the gas cap off? Just sounds to me like its creating a vacuum in the tank so you can't pull anymore gas. Then when you fiddle with the fuel system you let air back in and it fills the vacuum.

 

Put a fuel pressure gauge on the fuel rail's pressure test port and see if you are dropping fuel pressure (or lost pressure) when it starts to act up. You need to see what is going on when the problem is occurring.

I think the "tampering" you doing with the fuel system to get truck start may be coincidental (it may just be allowing enough time for cooling off - which is a common symptom of an overheated/failing electronic ignition module) but having the gauge connected will tell you for sure.