The present study investigated changes in acute serum hormone responses to a resistance exercise bout following a prolonged period of hypertrophic resistance training in young (YM) and older men (OM). Subjects performed a 5 × 10RM leg press exercise protocol before and after 20 weeks of hypertrophic resistance training. In YM, the acute responses in growth hormone were greater compared with before training (p < .05), and cortisol concentration did not increase after training. Endocrine responses in OM were similar before and after training. Greater acute growth hormone responses after training were associated with larger gains in lean mass in the entire subject group (r = .596, p = .019). These findings suggest that, in general, YM demonstrate greater adaptability within the endocrine system compared with OM. However, adaptability in growth hormone response was associated with larger training-induced gains independent of age.