Basal cell carcinoma is the most common form of skin cancer and is one in which both host and environmental factors are thought to play a role in its pathogenesis. For an investigation of the role of human leukocyte antigen (HLA)-associated variations in genetic susceptibility, thirty-one patients with multiple basal cell carcinomas were typed for HLA-A, B, C, and DR antigens. Patients were compared with both local and appropriate ethnic group controls. No statistically significant association with HLA-A, B, or C antigens was noted in any group. However, a significant increase in HLA-DR1 was noted in non-Irish, non-Ashkenazi patients. A tendency toward a decrease in HLA-DR3 was also noted among patients of Irish or Ashkenazi Jewish descent. The role of HLA-associated genetic factors in this form of skin cancer needs further investigation.