Resistance exercise has been shown to induce an acute hormonal response. The purpose of this study was to examine upper-body adaptations and the endocrine response to strength training in men and women when subjected to two different types of lower-body resistance training protocols. Nine males and eight females were assigned to either a Heavy Load (HL) (N = 10) or Mixed Load (ML) (N = 7) training routine three times per week for ten weeks. The HL-group executed low-volume, high-load resistance exercise for both lower and upper-body (4-6 reps at 80-90% of one repetition maximum (1-RM), three-minute inter-set rest). The ML-group performed the HL-protocol for the upper-body, but a high-volume, moderate-load protocol for the lower body (10-15 reps at 60-70% of 1-RM, one-minute inter-set rest). Volume load, 1-RM strength and hormonal measurements were analyzed by repeated-measures linear mixed models. Both groups increased their 1-RM in all assessments (p < 0.01) with no significant difference between groups at any time. Growth hormone (GH), testosterone and bioavailable testosterone (T/SHBG) increased in both groups during a standardized exercise session (p < 0.01) with ML having a greater increase in GH. The notion that acute elevations in anabolic hormones is important for muscle strength adaptation cannot be supported by the present study.