High-dose megestrol acetate has been associated with increased appetite and weight. To examine the effects of high-dose megestrol acetate in the treatment of anorexia and weight loss in patients with advanced hormone-insensitive malignant lesions, a randomized double-blind placebo-controlled trial was conducted. Patients receiving megestrol acetate for 1 month reported a significant improvement in appetite and adequacy of food intake compared with those receiving placebo. A three-item scale measuring appetite, adequacy of food intake, and concern about weight revealed a higher improvement with megestrol acetate than with placebo. Patients who worsened while receiving placebo had similar favorable changes after the cross over to megestrol acetate. These data indicate that megestrol acetate may improve appetite and food intake in patients with advanced cancer.