Serum antibodies to cytoskeletal systems were detected, using indirect immunofluorescence in patients with adult T-cell leukemia (ATL), healthy carriers of human T cell lymphotropic virus 1 (HTLV-1), patients with infectious mononucleosis and healthy adults. Healthy carriers of HTLV-1 had IgG antibodies to cytoskeletal systems as evidenced by an increased incidence of IgG antibodies to actin and vimentin. Decreased IgG antibody levels to Epstein-Barr virus nucleic acid (EBNA) were also evident. In patients with ATL, the titers of IgM antibodies to vimentin and cytokeratin showed a positive correlation with decreased serum levels of IgM, despite the fact that serum concentrations of IgM were significantly decreased in patients with ATL. The IgM antibody titer divided by the IgM concentration (the antibody ratio) was nigher than that of healthy carriers and healthy adults, suggesting that the IgM antibody response to cytoskeletal systems was preferentially preserved in these cases. There was also a suggestion of the presence of polyclonal as well as specific antibody responses to cytoskeletal systems in patients with infectious mononucleosis. As a result of these findings we suggest that there is some difference in the mechanisms responsible for the production of autoantibodies to cytoskeletal systems following HTLV-1 infection and Epstein-Barr virus infection.