The induction of antibodies in vaginal secretions by systemic (intramuscular) immunization in humans was investigated by using the tetanus toxoid vaccine. Five women, 30 to 40 years old, were injected with a currently used dose of toxoid (40 IU), and serum, saliva, and vaginal secretion samples were collected on day 0 and on day 6 or day 10. All of these subjects had been previously vaccinated at least 5 years before; four were in good health, whereas one suffered from AIDS in clinical category B3. In most cases, analysis of specific antibodies in the vaginal wash showed a dramatic rise after boosting. These antibodies were primarily of the immunoglobulin G (IgG) isotype. The specific activity (ratio of antibody titer to IgG concentration) was shown to increase after the booster injection, irrespective of variations in the IgG level during the menstrual cycle. Comparison between serum and genital antibodies showed no difference in terms of both specific activity and level of avidity. These results demonstrate that parenteral injections can induce a systemic-derived antibody release in the vaginal fluid. Hence, systemic vaccinations can be efficient at the genital level and thus could reinforce or even replace a local vaccine.