which would be better?

ok, I'm going to be doing a subwoofer install into a 2000 F-150. I will be running the Lightning Audio P2.350.1 amp and using 3 dual 6 ohm voice coiled subs. I have 2 combinations for this setup... combo #1: 3 JL Audio 8w6s, run in series/parallel so I present the amp with a 4 ohm load, or #2: 2 JL Audio 8w3d6's with a 12w3d6 wired in as well? I'm looking for a good thump in my F-150. Thanks guys!

stay with the same size speakers. If you didn't purchase the speakers yet then go with the 3 12".If you have the 8" already, then go with 3 8". I would stay with the same size

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SoundFX

I already own the 12w3d6 and a friend of mine has a pair of 8w3d6s...as for the 8w6s another friend of mine's selling his. Either way I wire them I'll get a 4 ohm impedence, which would you think would give me better sound?

Keep the 8" subs together don't throw in the 12" or vice versa.  If you combine different sub sizes then you run into the issue of mixing diffrent frequencies.  Is the box going to be ported or sealed?  I would just do one 12" JL and port the box.  That will give thump for you and others to notice.  Get the d4 12w3 and wire it in parallel to get 2 ohms.

With the one 12 you will be giving it enough power, if you go with the w6's espically 3 of them you will be far under power

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2009 0-1000 Trunk WR 154.0DB 2009 1001+ Trunk WR
2007 USACI World Champion
2007 World Record
2006 USACI Finals 2nd Place

Running multiple size subs off one amp is a no no. If you were using a seperate amp and could set your crossovers properly it would be a different story. I also gotta say that I agree with jeff on the underpower issue. What kind of music do you generally listen to, and if you say everything I will never answer you again :). But really, everyone always answers "I listen to everything" and that is almost always bullsh*t. A lot of people will listen to anything on some occasion but people generally listen to one or two styles on a regular basis so whats your poison.

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double-secret reverse-osmosis speaker-cone-induced high-level interference distortion, Its a killer

hm... 2 cu ft is the recomended size box for ported.  It's extended cab?  If it is do you want your back seat?  You might be able to put a 2 cu. ft box in under that seat w/out having to modify it but I couldn't tell you to be honest.  A ported would sound plenty loud but so would a sealed 12w3 being fed how-ever-much power.  The sealed would kick out more sq then spl.  Up to you but what ever you do stay the same size sub.

yup, extended cab. I'm planning on keeping the back seat in there. Also, I think I could get the 2 cu. ft. under there so that shouldn't be a problem. I'm thinking on just doing a sealed enclosure with my single 12w3d4. thanks for the help guys.