Mammoth is unlike any other track these guys race, so that may serve as somewhat of an equalizer.
As far as the Yammie riders (like MC) go, they could potentially ride just two bikes in three classes, as the 426 is legal in the 250s. So MC could go 4-stroke all day with the 250f and the 426f. I could be wrong about the 250 class, as their rules may be a bit more restrictive than AMAs.
I do think the altitude gives an advantage to the 'f's', given their larger displacments in their respective classes.