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I am on my 4th set of plugs on my nearly 58K mile car. The originals were Champions. Champions are kinda hard to find out my way. Don't ask me why. So, my second set, Autolites were fine until about 50K. Then I tossed in a set of NGK. Those were fine then I got a misfire. It tripped the CEL. I swapped them out for another set. Those didn't seem to run correct for the first 200 miles or so, then I dropped in a set of trusty old Autolites. My old DOHC car loved them. Now, after another 4,000 miles they are fouled and another CEL. So, right now I am running my slightly used NGKs.

Do I need to replace plug wires? They are Crane Fire Wires replaced about 25K-35K ago. Stock distribution block.

What could be the culprit?

Unfortunatly a misfire rarely has anything to do with the actual condition or performance of the spark plugs. Replacing them everytime an issue starts will only mask the true problem. Your problem could be any one of many things. A rich/lean mis could be caused by an air metering issue, tps, 02S, fuel injectors, timing, exhaust leak, and several mechanical internal problems as well. If it were a spark mis, a faulty coil, wires, plugs, or worst case scenario, a failing module might be the problem. For example, a stuck closed injector would cause an extremely lean condition in one cylinder. The 02 might add more fuel in an attempt to solve the issue, but a stuck injector is a stuck injector. This would be a constant misfire and the car would run horribly. If it's an intermittent problem, this is gonna be a fun one

Do I need to replace plug wires?

Yes.

i'd be changing the coil first thing.. since i've seen them do all kinds of wierd stuff..and usually thats the problem when your having misfires, unless your plugs/wires are in bad shape.. im not sure if you mentioned if the plug wires were new or not.. but the plugs are, so it would lead me to believe its either your wires or the coil.. you could also possibly have a bad upper o2 sensor, causing a rich mix, you getting bad mileage these days?

I am ordering a new set of MSD wires and matching coil (OOO! AAAHHH!) and doing up a new set of plugs again too. It keeps happening. It throws the CEL then moments later it will chug 3 or 4 times then be fine. My #2 cylinder wire is burnt up again. Tonight I am gonna fashion something togethe with a mix of older used stock wires, my used FireWires and a new set of plugs to hopefully get me through the weekend until Modern can get me my stuff. Noone locally sells anything of any quality for reasonable price so I am stuck at the mercy of mail order days before a major national holiday. GO ME! Add that to the fact that this is my only car and I drive about...oh...500 miles or more a week. I hope whatever I do works for a few days longer. I can't risk being fucked on the side of the highway.

run some injector cleaner through it - or even better, find some used injectors here and reaplce that #2 (does no one read what the tech-in-training suggested?) -- good info OB.

^^^
Agreed, replacing the plugs and wires all the time seem's to be masking the actual problem. My R/T a while back was having a severe issue with a #2 misfire and the tech ran cleaner through the system and replaced the #2 injector(covered under warranty).
The theory is because the fuel comes right into that side of the fuel rail, any deposits in the fuel gets dumped right there into injectors #1&#2 wich leads to a misfire since the injector is getting plugged.
Removing the fuel rail and cleaning it out might help a little bit too....

All right...might be the way to go as well. Might as well eliminate a whole bunch of stuff all at once. The car gets driven 20K+ a year. It could be anything at this point.