Long-term effectiveness of rubella vaccination in childhood is of particular importance because the ultimate goal of immunization is the prevention of infection during pregnancy. To determine how well vaccine-induced immunity persists in comparison to that acquired naturally, several hundred susceptible children who seroconverted after receiving HPV77DE5 vaccine were followed serologically over a 3-to-5-year period. The results indicate that vaccine-induced antibodies are less stable than those acquired through natural infection, and their persistence is closely related to the original response to immunization. Thus children who responded with a broad range of antibody types and who had brisk postvaccinal hemagglutination-inhibiting antibody titers of greater than or equal to 1:64, maintained such levels without significant decline. In contrast, among the children who had feeble hemagglutination-inhibiting antibody responses initially and failed to develop complement-fixing or precipitating antibodies, a significant proportion lost detectable hemagglutination-inhibiting antibody levels after 3 to 5 years. The current and future immunity of such children is therefore in doubt, unless natural reinfection with wild rubella virus or revaccination with a more effective vaccine corrects their antibody deficiencies.