An outbreak of Kaposi's sarcoma in homosexual men has recently been observed in New York and California which differs from the “classic” North American disease with regard to younger age of onset and clinical prognosis. Although the exact mechanism for initiation of either disease is still unknown, a viral mechanism has been suggested in both cases. In order to investigate the possible role of HLA‐as‐sociated variations in genetic susceptibility, 39 patients with histologically documented Kaposi's sarcoma were typed for HLA‐A,B,C antigens. Most of these patients were also typed for HLA‐DR antigens and for Gm allotypes. A significant increase in DR5 occurred in both groups. Decreases in B8 and DR3 and an increase in homozygosity for the Gm haplotype 3;5,13 were also noted. These results suggest that HLA and Gm linked immune response factors may play a role in the induction of both these forms of the disease.These studies were supported in part by NIH Grants CA‐08748 and CA‐22507. The authors also wish to thank Dr. Joyce Wallace, St. Vincent's Hospital, New York, for referring several of the Kaposi's sarcoma patients for study and to acknowledge the expert technical assistance of Cynthia Galloway and the expert typing and editorial assistance o