This study examined the impact of resistance exercise volume on myoD and myogenin in rodent quadriceps muscle. Six-month-old male Sprague-Dawley rats (316 +/- 2 g) performed either low-volume (LV; 10 sets x 10 contractions) or high-volume (HV; 20 sets x 10 contractions) resistance exercise at 75% one-repetition maximum. Muscles were analyzed for myogenin and myoD mRNA and protein expression 6, 12, 24 and 48 h post-exercise. In red quadriceps (RQ), myogenin mRNA was significantly elevated at 6 h following LV and this response was greater than HV at 6 h, while myogenin protein was significantly increased at 6 and 12 h following LV but only at 12 h following HV (P < 0.05). MyoD mRNA was increased at 6 and 12 h following LV and at 12 h following HV, while myoD protein was slightly decreased (LV; P < 0.05) or unchanged over time (HV). No changes were detected within the white quadriceps muscle. We conclude that acute resistance exercise can activate myogenin and myoD expression levels in RQ, but when exercise volume is doubled these myogenic responses are not proportional but delayed and blunted possibly because of excessive damage/injury. Further work is needed to determine the consequences of these specific myogenic responses on muscle hypertrophy following high-volume resistance exercise training.