Hey gang, relatively new user around here, but I've been browsing and reading a lot since aquiring my 2001 Blazer 4dr LT (4x4). I think I got a pretty good deal on it, considering it's got 100k and was showing a service engine light with the dreaded PO300 that nobody could seem to track down the cause of.

I wanted to share with the community what we eventually found to resolve the PO300, since in my researching and googling I have yet to see this as a culprit for someone else. Thought MAYBE this might help someone someday in their search for a resolution to their own PO300.

Anyway, the truck seemed to run just fine, but the service engine light stayed on, and when under heavy load at around 55mph (or higher) and 2500 RPM (or higher) the light would actually begin flashing.

Well, we went over the whole truck with a fine tooth comb (particularly 3 mechanics and myself), and of course opinions from even more mechanics. Scanner showed some serious misfiring in cylinders 1 and 4, but compression was good on all. Fuel pressure tested fine (but we'll get to that in a minute).

Well anyway, the plugs were pulled and were practically burnt up, so they were replaced. The wires didn't look bad, and no arching was noticed with the lights off, but nonetheless replaced them anyway. Did notice that one wire has some rust like foulage that matched up the to distributor cap. Replaced the cap and rotor as well, and the cap did have fouling on cylinders 1 and 4 (which seemed to go with what the scanner told us).
The fuel filter needed replaced anyway, so replaced it as well. Also, no vaccum leaks could be found either.

Anyway, nothing seemed to get rid of the misfiring and the SES light. But as days went on, the truck more and more often would give me trouble starting. After making several attempts, sometimes letting the truck sit for 5-10 minutes it would usually start up again.

Well, two days ago the truck finally got to the point it wouldn't start back. We knew the previous owner had recently had a used crankshaft position sensor put in it (from salvage yard), so went ahead and put a new one of those in as well. Truck was also idling kind of rough, so replaced a tested bad O2 sensor...but the truck still wouldn't start, although once we got it started it did idle a lot smoother.

So, up to this point we replaced:
Plugs (AC Delco Rapid Fires)
Plug Wires
Cap & Rotor
FUel Filter
02 Sensor (right above the cat)
Crankshaft Position Sensor
Put in K&N Cold Air Intake just for fun (wow...that REALLY woke this truck up, holy crap!)
Ignition Control Module (used one was put in by previous owner about a week before I bought it)

Then we noticed that sometimes we could turn the key on and hear the fuel pump kick in, but most of the time we couldn't hear it kick in. When we did hear it, we could start the truck, but if we didn't hear it, obviously the truck wouldn't start. So now we're thinking, "crap now we gotta put in a fuel pump too!?" Well the more we thought of this, on a hunch almost at the same time my buddy and I thought to check the fuse panels. Under the hood in the fuse/relay panel box we located the relay to the fuel pump...

I tried to start it, but it wouldn't. Then he applied some pressure to the relay, and I could start it. Then he would let off it, and it wouldn't start again. WTF!?

We pulled the relay, and it would actually rattle when shaken. Ran down to O'Reilys, picked up a $12 replacement and popped in it. It started right up, and after about 15 seconds or so, the SES went out and hasn't come back since. It's been driving and purring like a kitten the last couple days, now.
So I guess the fuel pump relay was just loose enough that the fuel pump was constantly kicking in and out, resulting in the random misfiring. I know, sounds crazy, but after $500 in parts (that honestly needed replaced anyway), a $12 fuel pump relay was the root of the whole problem.