Mammalian target of rapamycin and mitogen-activated protein kinase (MAPK) signaling pathways have been highlighted as important for muscle adaptations and thus, they may distinguish adaptations to different exercises. Typically, resistance exercise designed for muscle hypertrophy has moderate intensity (60–80% of one repetition maximum, 1 RM) while one prioritizing maximal strength with minor hypertrophy has a higher intensity (≥90% of 1 RM). Eight untrained men (28.4±3.7 years) conducted two different bilateral leg press exercise protocols: hypertrophic (5 × 10 RM) and pure maximal strength (15 × 1 RM) in a counterbalanced, cross-over design with 1 week between exercises. Vastus lateralis muscle biopsies were taken before and 0.5 h after resistance exercise, or in six controls (26.5±3.6 years) who rested. The phosphorylation of p70S6K (Thr421/Ser424), rpS6 (Ser240/244 and Ser235/236) and MAPK p38 as increased (∼2–16 fold) after both exercise protocols. However, the phosphorylation of MAPK Erk1/2 and p70S6K at Thr389 increased only after 5 × 10 RM. The increase in the phosphorylation of p70S6K (Thr421/Ser424), rpS6 (Ser235/236) and Erk1/2 were higher after 5 × 10 RM (P<0.05). No changes were seen in controls. In conclusion, MAPK signaling is greater after hypertrophic than maximal strength exercise protocol. This may mediate adaptations specific to these different types of training regimens.