In patients with human T-cell lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP), we investigated the significance of HTLV-1 specific antibodies in the cerebrospinal fluid (CSF). The quantities of HTLV-1 specific immunoglobulin G (IgG) in paired CSF and serum were evaluated by a sensitive enzyme immunoassay (EIA). The specificity of antiviral IgG was determined by radioimmunoprecipitation of HTLV-1 antigens. In 17 of 20 HAM/TSP patients, quantitative evaluation by EIA supplied evidence for antiviral IgG synthesis within the CNS. Radioimmunoprecipitation demonstrated IgG antibodies against HTLV-1 envelope and core proteins in all HAM/TSP CSF and sera tested. Regarding the 3 sample pairs indeterminate in EIA for intrathecal synthesis, 2 showed stronger precipitation of HTLV-1 antigens by CSF IgG than by equal amounts of serum IgG. Intrathecal antibody synthesis specific for both HTLV-1 core and envelope antigens is common in HAM/TSP, thus providing conclusive evidence for an immune response to HTLV-1 within the CNS.