CONTEXT: Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength. The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown. OBJECTIVE: To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss. DESIGN AND SETTING: Placebo-controlled, double-blind, randomized clinical trial conducted from September 1995 to July 1998 at a general clinical research center. PARTICIPANTS: Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L (349 ng/dL) and weight loss of 5% or more in the previous 6 months, 49 of whom completed the study. INTERVENTIONS: Participants were randomly assigned to 1 of 4 groups: placebo, no exercise (n = 14); testosterone enanthate (100 mg/wk intramuscularly), no exercise (n = 17); placebo and exercise (n = 15); or testosterone and exercise (n = 15). Treatment duration was 16 weeks. MAIN OUTCOME MEASURES: Changes in muscle strength, body weight, thigh muscle volume, and lean body mass compared among the 4 treatment groups. RESULTS: Body weight increased significantly by 2.6 kg (P<.001) in men receiving testosterone alone and by 2.2 kg (P = .02) in men who exercised alone but did not change in men receiving placebo alone (-0.5 kg; P = .55) or testosterone and exercise (0.7 kg; P = .08). Men treated with testosterone alone, exercise alone, or both experienced significant increases in maximum voluntary muscle strength in leg press (range, 22%-30%), leg curls (range, 18%-36%), bench press (range, 19%-33%), and latissimus pulls (range, 17%-33%). Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group. There was a greater increase in thigh muscle volume in men receiving testosterone alone (mean change, 40 cm3; P<.001 vs zero change) or exercise alone (62 cm3; P = .003) than in men receiving placebo alone (5 cm3; P = .70). Average lean body mass increased by 2.3 kg (P = .004) and 2.6 kg (P<.001), respectively, in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone (0.9 kg; P = .21). Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo. CONCLUSION: Our data suggest that testosterone and resistance exercise promote gains in body weight, muscle mass, muscle strength, and lean body mass in HIV-infected men with weight loss and low testosterone levels. Testosterone and exercise together did not produce greater gains than either intervention alone.