We studied two familial cases of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy from the Kii Peninsula, an area of endemic adult T-cell leukemia-lymphoma (ATLL) in Japan. Incidence of familial clustering of HTLV-I-associated myelopathy was about 20%. Type C retrovirus was isolated from cultured cerebrospinal fluid and peripheral blood lymphocytes in both cases. Modes of transmission seem to be similar to those described in ATLL, although there are no reports of both HTLV-I-associated myelopathy and ATLL occurring in the same family. We suggest three possibilities: (1) that the virus associated with HTLV-I-associated myelopathy is different from the virus causing ATLL, although they seem to be morphologically and immunologically similar; (2) that HTLV-I-associated myelopathy may be determined by the ATLL-causing virus plus a specific genetic background; and (3) some combination of factors 1 and 2.