To clarify the intrinsic factors involved in the manifestation of adult T-cell leukemia/lymphoma (ATL) in Japan, a third nation-wide study on ATL was conducted by the T- and B-cell Malignancy Study Group. General clinico-epidemiological findings on ATL and infectious modes of transmission of human T-lymphotropic virus type I (HTLV-I) from 181 ATL patients and their relatives were analyzed and the frequency of HLA antigens in 64 ATL patients was compared with that of 48 relatives of ATL probands, 340 controls from all Japan and 236 controls from Kyushu (Tanaka et al., 1984). General findings on ATL were mostly the same as those in the 2 previous nation-wide studies. The age-specific positivity rate of anti-HTLV-I antibody in siblings of ATL patients was markedly higher than that in children of ATL patients. This suggests that there is a high risk of mothers of ATL patients transmitting HTLV-I to their children who may develop clinical ATL after reaching ATL risk age. Frequencies of HLA antigens A26 and B39, among patients with ATL in ATL-endemic areas (Kyushu and South Shikoku), were higher (RR greater than 2.0 and p less than 0.05) than those of controls in Kyushu, and lower (RR less than 0.5 and p less than 0.05) with respect to A24, Bw46, Bw52, Bw61 and DR7. The frequency of Bw52 was also lower in relatives positive for anti-HTLV-I antibody than in relatives without antibody. However, these differences were not statistically significant after correction for the 45 antigens typed. These results can neither support nor refute the possibility of genetic susceptibility to HTLV-I infection and manifestation of ATL.