To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release.