Twenty-four patients with infantile spasms were entered in a double-blind, placebo-controlled, crossover study to compare the therapeutic effectiveness of ACTH (20 to 30 units/day) with that of prednisone (2 mg/kg/day). Response to therapy was determined by utilizing a comprehensive monitoring system and was defined as a complete cessation of spasms and disappearance of the hypsarrhythmic EEG pattern. A major difference between the effectiveness of ACTH and that of prednisone in stopping the spasms and improving the EEG pattern was not demonstrated. Nine patients responded to ACTH (five initial drug, four crossover), and seven patients responded to prednisone (four initial drug, three crossover). Twelve responded within two weeks of initiation of therapy, and four within six weeks. Therapy was tapered and discontinued immediately after a response was obtained. Five patients had a relapse; four responded rapidly to a second course of therapy. Of the eight patients who failed to respond to hormonal therapy, seven were given clonazepam with no improvement.