As I wrote in another thread: using all four RAM slots does lower down the three sticks at all due to changing from the faster tripple channel mode to a double channel mode, which means 25% lower clock frequenzy of the bus.
Not saying, that apps always go slower with using 4/8 sticks instead of 3/6 - it depends.
Have a look at
this again - especially memory riddle. When you use 3/6 sticks the system runs in triple channel mode (25,5GB/s) which is faster than dual channel mode (17GB/s) [sorry, have a
german link only]. Now using 4/8 sticks, the whole system will lower down in the dual channel mode.
But thats not the only point of interest. There ist another fact having influence on the total speed of the system. Mentioned by barefeats:
"As for memory usage, though you can only specify up to 3GB memory cache in the Performance Preference panel, Mac OS X is clever enough to grab unused memory as a virtual scratch volume instead before handing off the task to the actual scratch disk. If you are editing RAW photos with lots of layers and lots of history states, having the 8 memory slots in the 8-core Nehalem at dual-channel speeds can be better than 6 sticks running at triple-channel speeds. That's because slower memory transfers are better than really slow hard disk hits."
So some apps may benefit from using 4/8 sticks instead of 3/6 although the bus speed itself lowers down.
And at least "it's better to drop from triple channel to double channel performance than to run out of memory and start doing virtual memory disk swaps."