HTLV-I (human T-cell lymphotropic virus type I) is the retrovirus related to two distinct diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy (HAM). We analyzed the difference in antibody activities against the viral protein and the difference in specificities of anti-HTLV-I envelope antibodies among HTLV-I-infected individuals from the same HTLV-I-endemic area using a HTLV-I-gag-env hybrid protein and HTLV-I-env-encoded synthetic peptides as antigens, respectively. The difference in the responses of IgG anti-HTLV-I envelope antibody production among HTLV-I-infected individuals was qualitative as well as quantitative. Sera from patients with HAM showed significantly higher activities of antibodies against HTLV-I-gag-env hybrid protein than sera from other HTLV-I-infected individuals including ATLL patients. The specificities of IgG anti-HTLV-I-envelope antibodies, tested on seven synthetic envelope peptides, were directed mainly against four sites, V1E7 (residues 97-111), V1E8 (191-209), and V1E9 (268-286) on gp46 and V1E1 (342-363) on gp21. Three of these sites were shown to be immunodominant T-cell sites in mice in our previous study. Whereas patients in all categories made antibodies specific for V1E1 and V1E8, only HAM patients made antibodies to the V1E7 and V1E9 epitopes, suggesting a qualitative difference in response. Whether this difference is of pathogenetic significance is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)