PURPOSE: Studies that have attributed gains in lean body mass to dietary supplementation during RE training have not reported these changes alongside adaptations at the cellular and sub-cellular levels. Therefore, the purpose of this study was to examine the effects of two popular supplements; whey protein (WP) and creatine monohydrate (CrM) (both separately and in combination) on body composition, muscle strength, fiber-specific hypertrophy (i.e., type-I, IIa, IIx) and contractile protein accrual during RE training. METHODS: In a double-blind, randomized protocol, resistance-trained males were matched for strength and placed into one of four groups: creatine/carbohydrate (CrCHO), creatine/whey protein (CrWP), WP-only or carbohydrate–only (CHO) (1.5g/kg body wt/day). All assessments were completed the week before and after an 11 week structured, supervised RE program. Assessments included strength (1RM, three exercises), body composition (DEXA) and vastus lateralis muscle biopsies for determination of muscle fiber type (I, IIa, IIx), cross-sectional area (CSA), contractile protein and creatine (Cr) content. RESULTS: Supplementation with CrCHO, WP and CrWP resulted in significantly greater (P < 0.05) 1RM strength improvements (three of three assessments) and muscle hypertrophy compared to CHO. Up to 76% of the strength improvements in the squat could be attributed to hypertrophy of muscle involved in this exercise. However, the hypertrophy responses within these groups varied at the three levels assessed (i.e., changes in lean mass, fiber-specific hypertrophy and contractile protein content). CONCLUSIONS: Although WP and/or CrM appear to promote greater strength gains and muscle morphology during RE training, the hypertrophy responses within the groups varied. These differences in skeletal muscle morphology may have important implications for various populations and therefore, warrant further investigation.