The in vivo effects of saikosaponin, isolated from Bupleurum radix, on the immune responses are still poorly understood. We have already shown that saikosaponin-d increases phagocytic activities of murine peritoneal macrophages such as spreading activity, phagocytosis, lysosomal enzyme activity and intracellular killing activity of living yeast. This work extends these observations by showing that treatment with saikosaponin also increased the antibody response in plaque-forming cell numbers after in vivo immunization with sheep red blood cells (SRBC) and an augmentation of spleen cell proliferation responses to stimulation with T- or B-cell mitogens both before and after immunization. Furthermore, after SRBC immunization, the macrophages from mice treated with saikosaponin-d revealed significant increases in spreading activity and lysosomal enzyme activity. The chemiluminescences of the macrophages from mice treated with saikosaponin-d stimulated by opsonized zymosan and PMA were enhanced and interleukin-1 production by the cells was increased in a dose-dependent manner. These results demonstrate that saikosaponin-d may stimulate in vivo immunological lymphocyte functions, partly by activating some macrophage functions.