In this study the humoral antibody response in visna-maedi virus disease in sheep during long-term infection was analyzed utilizing immunoblot assays, neutralization tests and complement fixation tests. In immunoblot assays antibodies to several virus specific protein bands were detected, both against the viral envelope glycoproteins and internal proteins of the virus. The immunoblot reaction pattern resembled that found in HIV-1 infection in humans, consistent with reported similar molecular weight of the major proteins of these two viruses. The immunoblot band pattern was compared with the pattern of complement fixing and neutralizing antibodies through the preclinical and clinical course in natural and experimental cases of visna-maedi. Of six immunoblot bands identified as virus specific, the antibody response against three gag products and the major env glycoprotein appeared early in infection, at a similar time as the complement fixing antibodies. The response against two proteins, one presumably the transmembrane protein and the other possibly a gag precursor, was delayed.