The molecular mechanisms by which resistance exercise enlarges muscle mass, particularly the mass of fast-twitch type II fibers, are likely to involve enhanced phosphorylation/activation of key enzymes regulating protein synthesis. The hypothesis is that resistance exercise influences the phosphorylation of such key signaling proteins to a greater extent in type II than in type I fibers. Six recreationally active male subjects performed 4 sets of 6 maximal lengthening contractions with one leg. Muscle biopsies were taken from the vastus lateralis prior to and immediately after exercise and following one and two hours of recovery. Samples were freeze-dried and individual muscle fibers were dissected out and identified as type I or type II after staining for myosin ATPase. Phosphorylation of p70^S6k on Thr³⁸⁹ and S6 in type II fibers was increased 3-4-fold and 6-9-fold (P<0.05), respectively, one and two hours after exercise, whereas phosphorylation in type I fibers remained unchanged. Phosphorylation of Akt, mTOR and AMPK was unaltered in both fiber types, whereas that of eEF2 was attenuated 20-45% (P<0.05) in type II fibers during recovery. Phosphorylation of ERK1/2 was elevated 6-7-fold (P<0.05) immediately after exercise and p38 MAPK phosphorylation was increased 3-4-fold (P<0.05) for as long as one hour after exercise in both types of fibers, although the level was markedly higher in type II fibers (P<0.05). In conclusion, the elevation of p70^S6k and the reduction of eEF2 phosphorylation in the type II fibers following resistance exercise suggest stimulation of protein synthesis, which may contribute to a more pronounced enlargement of these fibers. Our findings also suggest that p70^S6k is activated, at least in part, via pathways not involving Akt-mTOR and MAPK.