There has been continuing interest in the development of synthetic and natural compounds which modify the immune response, particularly for the treatment of AIDS and cancer. Panax ginseng, employed for its putative medicinal properties in South Asia, was examined for its immunomodulatory properties in mice. A systematic evaluation of multiple immune system components revealed that Panax ginseng stimulated basal natural killer (NK) cell activity following subchronic exposure and helped stimulate recovery of NK function in cyclophosphamide-immunosuppressed mice but did not further stimulate NK activity in poly I:C treated mice. Other immunological parameters examined, including T and B cell responses were not affected. Panax ginseng provided a degree of protection against infection with L. monocytes but did not inhibit the growth of transplanted syngeneic tumor cells. Increased resistance to L. monocytogenes was not detected in challenged mice previously given immunosuppressive doses of cyclophosphamide. Taken together, these data suggest that Panax ginseng has some immunomodulatory properties, primarily associated with NK cell activity.