Serologic HLA typing was performed on 29 patients with infantile spasms and hypsarrhythmic patterns in their electroencephalograms (EEGs). There were no significant increases in the frequencies of HLA-A, B, and C antigens in the infantile spasm group as compared with controls. However, there was a significant increase in the frequency of DRw52 in the infantile spasm patients (90%) as compared with controls (72%) (p less than 0.05). In addition, 3 of 12 white infantile spasm patients demonstrated the complete B18,DR3 (DRw52) haplotype; none of 150 control white subjects showed this haplotype. These findings contribute to evidence that immunological mechanisms may be involved in the pathophysiology of infantile spasms.