Unaccustomed exercise is followed by delayed-onset muscle soreness and morphological changes in skeletal muscle. Animal studies have demonstrated that women have an attenuated response to muscle damage. We studied the effect of eccentric exercise in untrained male ( n = 8) and female ( n = 8) subjects using a unilateral exercise design [exercise (Ex) and control (Con) legs]. Plasma granulocyte counts [before (Pre) and 48 h after exercise (+48h)] and creatine kinase activity [Pre, 24 h after exercise (+24h), +48h, and 6 days after exercise (+6d)] were determined before (Pre) and after (+24h, +48h, +6d) exercise, with biopsies taken from the vastus lateralis of each leg at +48h for determination of muscle damage and/or inflammation. Plasma granulocyte counts increased for men and decreased for women at +48h ( P < 0.05), and creatine kinase activity increased for both genders at +48h and +6d ( P < 0.01). There were significantly greater areas of both focal ( P < 0.001) and extensive ( P < 0.01) damage in the Ex vs. Con leg for both genders, which was assessed by using toluidine blue staining. The number of leukocyte common antigen-positive cells/mm2 tissue increased with exercise ( P< 0.05), and men tended to show more in their Ex vs. Con leg compared with women ( P = 0.052). Men had a greater total (Ex and Con legs) number of bcl-2-positive cells/mm2 tissue vs. women ( P < 0.05). Atrophic fibers with homogeneous bcl-2-positive staining were seen only in men ( n = 3). We conclude that muscle damage is similar between genders, yet the inflammatory response is attenuated in women vs. men. Finally, exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle.