To evaluate the relation between histocompatibility antigen phenotypes and solid malignant neoplasms, HL-A type was determined in 633 cancer patients and compared with those of 489 normal controls. HL-A8 was elevated in patients with squamous cancer, melanoma, and adenocarcinoma. The highest incidence occurred in patients with salivary gland adenocarcinoma (67% vs only 17% in normal controls). A threefold increase in HL-A5 was detected in patients with connective tissue sarcomas (28% incidence vs 9% in normal controls). Antigen frequencies did not vary when analyzed by time of diagnosis or interval after treatment. The finding that certain malignant neoplasms have associations with increased frequency of individual HL-A antigens may give clues to cause and genesis for these tumors.