The human T-cell leukemia/lymphoma virus (HTLV) is a novel Type-C retrovirus isolated from patients with post-thymic T-cell malignancies. Thirteen patients diagnosed in the United States were identified as having antibodies to HTLV and a typical clinicopathologic syndrome characteristic of adult T-cell leukemia/lymphoma as described in Japan. The most characteristic diagnostic feature in our series was the presence of highly pleomorphic and lobated lymphoid cells in the peripheral blood. Also notable was acid phosphatase activity which was partially tartrate-resistant in the neoplastic cells. The pathologic spectrum of the associated lymphomas was broad and encompassed several diffuse histologic subtypes in the Rappaport classification, the working formulation, and the classification of the Japanese lymphoma study group. However, differences in survival could not be correlated with differences in histologic subtype. All patients presented with Ann Arbor Stage IV lymphoma. Other common clinical features were generalized lymphadenopathy, hepatosplenomegaly, skin and peripheral blood involvement, hypercalcemia, and lytic bone lesions. The clinical course was aggressive with a median survival of 9 months. In two-third of patients with cutaneous involvement, epidermal infiltration resembling Pautrier microabscesses was observed. However, most cases can be readily distinguished from mycosis fungoides/Sézary syndrome on clinical and epidemiologic grounds. The presence of HTLV-antibodies in patients with lymphoid malignancies appears to define a distinct clinicopathologic syndrome which tends to occur in geographic clusters. Adult T-cell leukemia/lymphoma is favored as the diagnostic term for this clinicopathologic entity.