The 250 is in a 68 truck with lots of miles. Engine is covered in a thick coat of crud so the engine hasn't been apart in long time if at all. #5 cylinder doesn't fire at low speeds but when the engine is reved it runs on all six. I can feel it and hear it at the exhaust pipe, misfire and then sounds very smooth when reved. I shorted the spark plugs and confirmed it's number 5.
Points ignition and it all seems ok with the usual slightly sloppy distributor shaft. Engine starts instantly but when cold runs very poorly (like only on 4 cylinders) until it gets some temperatures. It has a stock hand choke and I know how to use it One warmed up it idles steady with the number 5 misfire.
The past owner tried to fix it and in the process replaced the tune up parts and put on a correct factory rebuilt carburetor.
I checked the compression, the cylinders are between 105-120 PSI, with number 5 being 105 psi along with a another one. Low but enough to fire the cylinder.
I adjusted the valves. The head was quite clean and all rockers were moving ,push rods spinning and oil flowing . When backing off the rocker until it clicks, the engine seems to run smoother. Tighten the rocker nut slowly just to the point of eliminating the clicking and the idle gets rougher...and will stay this way despite not being tighten down the usual 1/2- one turn more. Number 5 does this as well as number one cylinder but number one doesn't misfire.
Vacuum gauge reads pretty steady at 16 inches at a 500 rpm idle with the timing set at 4 degrees. Rev the engine and the vacuum drops to 5 and then 22 and the engine comes back to idle.. But just as the engine returns to idle the gauge needle fluctuates between 16-17 inches and stays that way for maybe 5-10 seconds before going back to a steady 16 inches at idle.
There's no vacuum leaks to be found and only a PCV and ported distributor vacuum.
No excessive blowby or exhaust smoke.
Because of the strange lifter reaction to adjustment I'm thinking there's a few lifters pumping up at idle speeds and one pumps up enough to hold open a valve on number 5...But the vacuum gauge needle should have been dropping on that cylinder... What do you think?? Thanks

Try a new lifter in the #5 valve[s] that have the adjustment issue. I have had this issue too on old tired sixes and SOMETIMES this fix works. If the engine is that tired, it doesn't even have to be a new lifter, just a known good lifter that is still convex or flat (but not concave) will do. Even the difference between 105psi 120psi can indicate this problem.

Could also be a cracked valve spring - similar subtle change in compression check and it will "seem" to hit all 6 off idle.

Could also be a vacuum leak, but then it seems #6 would also skip now and then.

Also try swapping plugs and plug wires and see if the miss moves cylinders.

ITS THE COMMON CHEVY 6 PROBLEM, ITS A LEAKING INTAKE MANIFOLD GASKET. TAKE SOME STARTING FLUID AND SPRAY WHERE INTAKE BOLTS TO CYL. HEAD AND IT WILL REV UP. TRY IT................

Previous owner replaced the intake gaskets and my spray tests and the vacuum gauge says no leak. And what was said above about 5 & 6 sharing an intake runner.
I need to have a close look again at the distributor . These engines are known to experience worn distributor shaft bushing that affects dwell...

The problem is fixed.. Weak valve springs were allowing a few lifters to pump up and hold the valve open at low speeds. And a few sticky lifters. I replaced all the lifters and springs as a precaution...I noticed during the spring replacement the cylinders held air pressure with very little leakage, I was suspecting leaky rings and valves...

Wow, valve springs? Musta been pretty tired!

Did you check the loads at installed height of the old tired ones to find the culprits?

No, I just pressed on the rockers with my hand. The first 1/8 inch of spring travel was like a wet noodle..One guy out of dozens who responded to the engine problem on several websites got it right. He said in fleet service the springs would fade away an allow lifter pump up at idle.