Fifty patients in whom the diagnosis of infantile spasms had recently been made and who had hypsarrhythmic electroencephalographic findings were randomly assigned to receive either high- or low-dose therapy with corticotropin (adrenocorticotropic hormone; ACTH). Twenty-six patients receiving the high-dose therapy were treated as follows: 150 U/m2 per day for 3 weeks, 80 U/m2 per day for 2 weeks, 80 U/m2 every other day for 3 weeks, and 50 U/m2 per day every other day for 1 week, with the dosage then tapered to zero during a 3-week period. The 24 patients assigned to the low-dose therapy group received 20 to 30 U/day for 2 to 6 weeks; the dosage was then tapered to zero during a 1-week period. Population characteristics (cryptogenic vs symptomatic, treatment lag, and age at start of treatment) of the two groups were similar. Response, defined as cessation of spasms and disappearance of hypsarrhythmia, was determined objectively by serial prolonged video and polygraphic monitoring studies. Of the 26 patients treated with the high-dose therapy, 13 (50%) responded; of the 24 patients treated with the low-dose therapy, 14 (58%) responded (p value not significant). No significant difference in the relapse rate between the two groups was observed. The side effects seen in both treatment groups were similar, except that hypertension occurred more frequently in the high-dose group. These results indicate that there is no major difference in the effectiveness of these two regimens in the treatment of infantile spasms with respect to spasm cessation and improvement in the patients' electroencephalographic findings.