During a prospective double-blind, crossover study of ACTH versus prednisone therapy, serial computed tomography (CT) scans were performed on 16 children with infantile spasms. Pre-treatment scans revealed four findings: normal (6 patients), generalized atrophy (bilaterally enlarged ventricles and/or subarachnoid space) (2 patients), predominantly focal atrophy (3 patients), and congenital anomalies (5 patients). Within 2 weeks of initiating relatively low therapeutic dosages of ACTH or prednisone, a significant number of the infants (63%) had CT findings consistent with decreased cortical volume; in many cases (44%), these findings had not reversed 4 to 6 weeks after discontinuing therapy. Duration of therapy did not correlate significantly with the persistence of CT changes.