Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestation including adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases, however, infected patients remain asymptomatic. The participation of the immune system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG antibody response of HTLV-I-infected individuals has been investigated using both ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be recognized by antibodies from patients with various systemic autoimmune diseases, and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The results were compared with the reactivity of sera from individuals with non-HTLV-I-related neurological diseases and healthy blood donors. Raised levels of autoantibodies reacting with several nuclear and cytoplasmic antigens were found in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals, both the prevalence and level of IgG antibodies were lower and directed only against a restricted set of antigens. The mechanism of induction of these antibodies still remains obscure. However, the results show that a significant autoimmune response exists in these patients and it may contribute to the pathogenesis of the disease.