We have examined the immunosuppressive effects of representative ginsenosides (Rb1, Rb2, Re and Rg1) from Panax ginseng C. A. Meyer on CD4+ and CD8+ lymphocyte proliferation. Ginsenosides differentially modulated lymphocyte proliferation induced by concanavalin A (Con A), lipopolysaccharide (LPS), phytohemaglutinin (PHA) and interleukin-2 (IL-2). Thus, Rb1 and Re significantly enhanced Con A-induced lymphocyte proliferation, whereas Rg1 did not affect the proliferation. Interestingly, however, Rb2 strongly blocked Con A, LPS and PHA-induced lymphocyte proliferation with the IC50 values of 21.8, 29.0 and 24.0 microM, respectively. Moreover, Rb2 inhibited Con A-stimulated IL-2 production with an IC 50 of 13.3 microM. In the IL-2-stimulated CD8+ T cell (CTLL-2) proliferation assay, Re and Rg1 showed strong suppressive effects with IC50 values of 57.5 and 64.7 microM, respectively. In contrast, neither Rb1 nor Rb2 did inhibit CTLL-2 cell proliferation at tested concentrations. These results suggest that ginsenosides from P. ginseng may modulate lymphocyte proliferation in a different manner.