We have developed a novel, sensitive and efficient radioimmunoprecipitation assay (RIPA) which provides an alternative to the Western blot for characterizing antibodies against HIV-2. The assay is based on a radioiodinated antigen consisting of a soluble preparation of the NIH-Z (HIV-2) strain of 1000X purified virus spiked with purified recombinant HIV-2 gp105/110. Radiolabeled proteins were immunoprecipitated by immune human sera, even at the early stages of seroconversion. This method is more sensitive, has equivalent specificity, and is more efficient than Western blotting. Most importantly, the viral proteins labeled with Bolton-Hunter reagent are well suited to biochemical studies.