Involuntary weight loss is a frequent complication of acquired immune deficiency syndrome (AIDS) and ultimately affects the majority of patients. The deleterious effects of weight loss on immune function and the physical and psychological sequelae of severe weight loss are well recognized. Megestrol acetate induces appetite stimulation and nonfluid weight gain in patients with advanced hormone nonresponsive cancers. In a pilot study, megestrol acetate produced nonfluid weight gain in patients with AIDS. Two double-blind randomized placebo-controlled trials of megestrol acetate for the treatment of AIDS-related anorexia and cachexia have shown improvements in body weight with treatment. In a multicenter trial reported by Flynn et al. at the 7th International Conference on AIDS (1992), 65 patients with AIDS and weight loss of > 10% of ideal body weight were randomized to placebo or megestrol acetate 800 mg/day. Megestrol acetate-treated patients had a significantly greater mean maximum weight gain (p = 0.027) and appetite stimulation (p = 0.021) than did placebo-treated patients. In a second, larger randomized placebo-controlled trial, 271 patients with AIDS, anorexia and cachexia were randomized to receive placebo or multiple doses of megestrol acetate at 100, 400 or 800 mg/day for 12 weeks. A maximum weight gain of at least 5 lb (2.25 kg) was observed in 64.2% of patients in the 800-mg megestrol acetate group compared with 21.4% in the placebo group (p < 0.0001). Mean maximum weight change from baseline to last evaluation was +8.3 lb in the 800-mg group and -1.1 lb in the placebo group (p < 0.001). Mean change in lean body mass from baseline to last evaluation was +2.5 lb in the 800-mg group versus -1.7 lb in the placebo group (p < 0.001). A significant improvement in appetite was seen in patients receiving 800 mg megestrol acetate compared with patients receiving placebo. No significant toxicity was observed with megestrol acetate therapy. Megestrol acetate is an effective treatment for some patients with AIDS-related anorexia and cachexia.