The purpose of this study was to compare the effects of different between-set rest periods (1 and 2.5 minutes) on changes in hormone response, strength, arm cross-sectional area (CSA), thigh muscular cross-sectional area (MCSA), and body composition during a 10-week training period. Twelve untrained males (24.8 +/- 5.9 years) engaged in resistance training using either 1 minute (short rest [SR], n = 6) or 2.5 minutes (long rest [LR], n = 6) of rest between sets, with a load that elicited failure on the third set of each exercise. Body composition, thigh MCSA, arm CSA, and five-repetition maximum (RM) squat and bench press were assessed before and after training. Blood samples were collected after exercise in weeks 1, 5, and 10. In week 1, postexercise plasma testosterone levels were greater in SR (0.41 +/- 0.17 mmolxL) than in LR (0.24 +/- 0.06 mmol x L, p < 0.05), and postexercise cortisol levels were greater in SR (963 +/- 313 mmol x L) than in LR (629 +/- 127 mmol x L, p < 0.05). Week 1 postexercise GH levels were not different (p = 0.28). The differences between hormone levels in weeks 5 and 10 were not significant. Arm CSA increased more with LR (12.3 +/- 7.2%) than with SR (5.1 +/- 2.9%, p < 0.05). There were no differences in strength increases. These results show that in healthy, recently untrained males, strength training with 1 minute of rest between sets elicits a greater hormonal response than 2.5-minute rest intervals in the first week of training, but these differences diminish by week 5 and disappear by week 10 of training. Furthermore, the hormonal response is highly variable and may not necessarily be predictive of strength and lean tissue gains in a 10-week training program.