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Q: P0300 Random misfire on 1998 Chevrolet S10

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I change out the ignition coil;fuel filter, wires,PVC,plugs,rotor & cap and air filter,clean thottle body check for vacuumm leaks. the codes was reset after driving for about 20 miles check engine light came back on check code same P0300 Random misfire
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Many things can cause such an issue, but the one issue that is solely S-10 related is that the earlier-model poppet-style fuel injectors used in the '96-and-up model year Vortec engines were prone to sticking open or sticking shut after a large mileage buildup. Gm was even forced to address the issue in the early '00's by updating the injector style. The new injectors had the same flow rate, but were designed in such a way as to alleviate the problems found in the earlier ones.
There was even a forced recall/replacement in the state of CA due to a lawsuit by the EPA in that state, claiming the poor design was leading to a higher-than-average rate of emissions testing failures in the above-described model years.
This is oftentimes the culprit in the 4.3 engines when all the other standard solutions have been exhausted, ie: spark plugs, wires, cap and rotor, etc..

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I have a 2000 S10 Blazer, 4.3, 4 door 4x4. Had p0300 code that would not go away. Changed all of fuel system, ignition system,and still had problem. A friend told me these trucks have an air pump and check valves connected to the exaust manifolds. I had no air pump codes so I changed the check valves and this fixed my random misfire code. Hope this helps as another possible solution.
Can you feel the engine misfire? Any other codes? Which engine is in your S10? Manual or automatic transmission?
It look like you have taken care of the ignition possibilities. There still could be a mechanical fault - check compression. Or a fuel injector or injector signal fault. If you can feel the misfire, monitoring the engine with a quality scan tool should help pinpoint the cylinder causing the misfire.
As I have learned through trying to figure out my problem, a bad mass air flow sensor can cause misfire codes, sense it regulates and measures the amount of air that passes through, the three main components of a running engine is fire, fuel, and air, to much or too little air can cause all the problems that you have discribed, also the mass air flow sensor is notorious for going out on these engines
i would ck the popit nosil injectors(octo-puss style) thats the number 1 problem i have had with them sense day one
I had the same problem, went thru four mechanics-ASE, Dealer, local shops, etc. Finally backyard mechanic found the fuel injector control module was shot, replaced it and it runs great.
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