The presence of HLA-associated genetic factors in patients with multiple skin carcinomas was investigated. 43 patients affected by multiple basal and squamous cell carcinomas and 220 healthy age-matched controls were typed for 72 HLA-A, B, C, DR antigens. A negative association of B-17 (mostly B-58) and a positive association of Cw-3 and DR-1 was observed in patients with multiple basal cell carcinomas; a similar negative association with B-58 and positive association with DR-1 was seen in patients with squamous cell carcinomas. The results of this study suggest the presence of resistance factors to the development of skin cancers associated with B-17 (B-58) antigen.