We were unable to identify an antibody to either HTLV-I or HIV-1 in patients with multiple sclerosis (MS) by ELISA, by radioimmune assay, or by radioimmune precipitation techniques. Immunoblot studies for HTLV-I-specific antibodies revealed faintly reactive bands in 2 of 44 MS patients but not in patients with other neurologic diseases. We did not find seroreactivity to HIV-1 or to the distantly related retrovirus, caprine arthritis encephalitis virus (CAEV). These findings suggest that MS is not related to infection by human retroviruses with antigenic similarity to HTLV-I, HIV-1, or CAEV.