Ten eumenorrheic women (age 24.1 ± 4.3) performed 2 randomly assigned heavy-resistance exercise protocols (HREP) on separate days during the early follicular phase of the menstrual cycle. Multiple-set (MS) HREP consisted of 3 sets of 10 RM of 8 resistance exercises with a 1-min rest between exercises and sets. Single-set (SS) HREP consisted of 1 set of 10 RM of the same 8 exercises in the same order, with 1-min rest between consecutive exercises. SS total work was about one-third that of the MS. Immunoreactive serum growth hormone (GH), cortisol, and blood lactate were measured pre- and postexercise (0, 15, and 30 min). The MS produced significant (p < 0.05) increases in serum GH and cortisol above resting levels at all postexercise times. The SS significantly increased serum GH at 15 min postexercise, and cortisol at 0 and 15 min postexercise. Both protocols yielded significant increases in blood lactate above rest at all postexercise times. The MS produced the most significant hormonal and metabolic responses, indicating that exercise volume may be an important factor in hormonal and metabolic mechanisms related to resistance exercise in women.