Hey gang. I have been fighting a P0300 general misfire for awhile now. My mechanic did a clean out of the injectors and fuel system. Ran better for awhile, but its back. No particular time or weather or temperature related. However, it does seem more likely to kick in if I use tow/haul mode. The cel comes on flashing for about a mile or so, then goes out. The P0300 always shows up as a pending code.
Truck has 91k on it, 5.3L, 4WD. Any clues where to look next? My mechanic checked over the plugs and ignition. Seems to be related closely to using the tow/haul when going up and down hills on backroads on my way to work. It hasn't set off while not in tow/haul yet. I wonder why it only seems to do it in that setting? I don't tow anything yet, but that setting seems to be easier on the trans when I'm on the backroads. All its doing is holding the gears longer and keeping the converter unlocked. I'm not putting a bigger load on it. So I have no idea why is only happens when its in the other mode.

if the ign has been checked next for me would be to check fuel pressure, lack of pressure from pump, filter, or regulator.

Coils, plugs and wires are typically the first things to check. If your mechanic was thorough in checking these out the next area to check is everything related to fuel pressure. If you have not changed the fuel filter in a while, start with that. Next, have your mechanic check fuel pressure at the rail versus spec pressure for your engine. If pressure is low, you could have a tired fuel pump. This could cause random misfires.

Once you rule out spark and fuel, you may be into a mechanical issue such as a broken valve spring.

Wow, I had almost forgotten about starting this thread! Searched a Silverado Misfire, and there it is...
Been really busy, with life, work, etc, but glad to see this site is still up and running!!

Still throwing this code, even 3 years later.. who knows why.
Haven't really done any modifications to the truck. Just kinda kept it going, so haven't changed anything that should affect it.
Tow/Haul still sets it off
Manual shift into 3rd or 2nd sets it off
Will never misfire if left in OD and out of tow/haul.
Had a few people look at it, make computer recorded test runs with it, yet somehow it still persists.
Is it even possible that the computer needs to be reprogrammed? That somehow the program is corrupted, which is only set off by the transmission being in an alternate program mode?
I'm perplexed.
Was hoping it would either sort itself out in time, or whatever the problem is, would get worse and I could figure it out, but I'm still just as stumped as I was when I started this post.
Anyone?

Tow/haul uses different set of tables in the programming. Everything from how long the trans stays in each gear, trans line pressure, and it even has a different program for how the engine runs. With that said, if the engine is told to work harder using the tow/haul and your ignition system isn't up to par, then you could experience a P0300.

Even though you are at 91K, 100K is NOT the magic number for your first tune up. Ignition components can fail out of the box. I suggest a full tune up of plugs and wires.

Still could be secondary ignition.....towing creates a greater "load" on the system.......

For example, on most GM cars, you tend to feel that misfire, when the TCC engages in fourth gear, while slightly accelerating up a grade......step on the gas, and the TCC disengages, load, decreases, and the misfire is gone....

^Exactly

Thanks guys. But actually, now the truck has almost 140k on it. Did exactly the same thing as it did with 91k. No worse, no better.
It does seem to be better in colder weather. Since we've been hovering around 0 the past week for highs, it seem to take longer to trip that code. I do drive around in 3rd, especially on the back roads, and the colder it is outside, the longer it will take to trip. Some days driving into work, it never sets.
As far as the load is concerned, I don't actually tow anything. But, even if I have the truck playing in the snow in full 4x4, it doesn't trip the code as long as I don't put it in 3rd. Also, I did notice that on long downhill stretches, if I use 3rd for engine braking, without touching the gas, it doesn't trip the code either.

take a look at the TB blade on the back too and see if it looks carboned up