Human leukocyte antigens (HLAs) play an important role in regulating the immune response to infectious agents and determinants of malignant transformation. We compared the HLA frequencies of 25 black patients with adult T-cell leukemia/lymphoma (ATL) referred to the National Cancer Institute for therapy with a racially similar, asymptomatic control population of human T-cell lymphotrophic virus, type I (HTLV-I)-seropositive individuals (n = 45). Serological typing was performed for MHC class I and II antigens. Antigen frequencies were calculated, and corresponding gene frequencies were estimated using the maximum likelihood method. Comparisons between the ATL and control group were made with chi 2 or Fisher's exact test. Three antigens (A36, B18, and DR53) were found to have a higher frequency in the ATL patients than in the controls (uncorrected two-tailed P < 0.05). The gene frequencies for these antigens also were statistically significant in the uncorrected analysis. However, only A36 approached statistical significance after correction of the P value for multiple comparisons (P = 0.08). The results of this pilot study indicate that black patients with ATL may have increased frequencies of certain class I HLA when compared with a racially similar HTLV-I-positive reference population. This suggests that either these antigens may represent markers for a population at greater risk of developing ATL once infected with HTLV-I or that they were acquired at some point in the process of malignant transformation or progression from the carrier state to onset of ATL. These antigens should be targeted in larger studies to confirm or refute these findings.