In Japan, adult T-cell leukemias and lymphomas are more common than in the United States and Europe, and in the southwest part of Japan these T-cell malignancy cases appear in clusters. Therefore, we investigated the involvement in these leukemias and lymphomas of the human T-cell leukemia virus (HTLV) that was previously isolated in one of our laboratories from cultured T cells of some patients in the United States with leukemias and lymphomas involving relatively mature T cells. High titers of antibodies capable of quantitative precipitation of (125)I-labeled p24, a well characterized core protein of HTLV, were detected in 12 of 12 patients with untreated adult T-cell leukemia (ATL). (One negative was a patient on chemotherapy.) Ten of the 12 positive samples were from an area where the disease is endemic. Strong precipitating antibodies were also detected in five of seven cases of T-cell malignant lymphoma (TML) which differs from ATL by having fewer leukemic cells in the peripheral blood. High antibody titers were also observed in one of five cases of acute monoblastic leukemia and one of eight cases of chronic myelogenous leukemia in the blast phase of the disease. Low to moderate titers of antibodies were detected in several categories of leukemia (two cases of blast-phase chronic myelogenous leukemia, two cases of acute lymphoblastic leukemia of the null-cell type, and one case of acute myelogenous leukemia). Among all categories of leukemias, except ATL and TML, more cases were negative than positive for anti-p24 activity. All of 79 sera from normal Japanese, including 39 collected from the endemic ATL area of southwest Japan, were negative for antibodies to HTLV p24. All the positive reactivities observed were highly specific to HTLV. The only competition observed in the precipitation of HTLV p24 was with HTLV or with cell lines expressing HTLV and not with various animal retroviruses or a large number of human and subhuman primate cell lines, not known to be producing HTLV. The data strongly indicate an association of HTLV with the increased incidence of ATL in parts of Japan, probably with other forms of leukemias in Japan, and, less commonly, with certain T-cell malignancies in the United States.