Orally fed Quillaja saponins amplified the immunopotentiating ability of an intraperitoneally (IP) administered inactivated rabies vaccine in mice. The number of animals surviving rabies infection was markedly higher (90-100%) in groups of animals receiving a combined treatment of oral saponin (SAP) and IP vaccine, compared to groups receiving vaccine alone (25%), or to unimmunized mice (0%). Antibody production was significantly higher in animals fed SAP 2 weeks after primary or secondary sensitization with an IP-injected vaccine. In mice given 2 IP doses of vaccine, 1 week apart, simultaneous feeding of SAP resulted in an enhanced production of rabies-specific (whole Ig) antibodies. On the other hand, animals preconditioned with SAP 3 days prior to administration of the vaccine exhibited greatly increased IgG antibody levels. Moreover, SAP-preconditioned mice vaccinated with a very low dosage produced significantly higher levels of antibodies.