A strain of mouse transgenic for the env gene of the HIV-1 virus was used to study the immunogenicity of a gp160-derived vaccine (the protein encoded by the HIV env gene) and its effect on disease progression. Untreated transgenic mice frequently developed a rapidly progressive renal disease similar to that affecting approximately 10% of HIV-infected humans. When transgenic mice were immunized with recombinant purified gp160, their edema, proteinuria, and serum BUN levels were substantially reduced and their survival prolonged (p < 0.01). The increased longevity of immunized transgenic mice correlated with the production of IgG antibodies reactive with gp160.