Antibodies specific for human T-cell leukemia-lymphoma virus type I (HTLV-I) were demonstrated in serum samples from various groups of people in South Africa, Uganda, Ghana, Nigeria, Tunisia, and Egypt. The samples had been collected for other purposes and were presumably selected without bias toward clinical conditions associated with HTLV infections. Regional differences in antibody positivity were observed, indicating widely distributed loci of occurrence of HTLV on the African continent in people of both black and white ancestry. Two patients with high titers of antibody to HTLV-I had some signs of adult T-cell leukemia-lymphoma. In several groups a high frequency of false positive serum reactions was indicated when specific confirmation steps were included in the assay. Further characterization of these sera revealed highly elevated immunoglobulin levels, possibly due to polyclonal activation of immunoglobulin synthesis in these subjects. The possibility that related cross-reactive human retroviruses coexist in the same groups was not eliminated.