The stoichiometry of human immunodeficiency virus type 1 (HIV-1) inactivation by soluble receptor CD4-IgG hybrid dimers (CD4-IgG) was examined. The extent of HIV-1 inactivation was measured in a sensitive plaque-forming assay, and the corresponding level of CD4-IgG binding was determined by immunofluorescence of infected cells. Ninety percent virus inactivation occurred at relatively low levels of CD4-IgG binding (10% of the saturating level). At even lower binding levels (1.4% of maximum binding), virus survival was 44%. Over a broad range of binding conditions, the survival curve followed a model in which viruses binding more than a threshold level of CD4-IgG were completely inactivated, while viruses binding less remained infectious. The data indicate that CD4-IgG binding to 1.4% of gp120 binding sites equals the threshold for inactivation. Thus, virus inactivation can begin when 3 CD4-IgG (of approximately 216 gp120 sites) bind per virion.