Deoxynupharidine (DON) is an alkaloid isolated from rhizome Nuphar pumilum which has been extensively used in the treatment of rheumatoid arthritis and back and leg pains as a folk remedy in China. Data presented in this paper indicate that the DON has potent immunosuppressive activities. Mitogens or allogen induced lymphoproliferative responses of murine splenocytes or human tonsillar mononuclear cells (hTMNC) were markedly reduced when DON was added in the cultures. The trypan blue exclusion test showed that this inhibition was not exerted through a toxic effect. IL-2 activity in the supernatants was evaluated for its ability to support IL-2 independant cell line (CTLL-2) proliferation and the results showed that DON had no marked effect on IL-2 level, but inhibited the capacity of murine peritoneal macrophages to produce IL-1 and TNF, which play very important roles in the process of inflammation and immune response. This immunosuppressive actions of DON may partly account for some of its potential in the treatment of chronic inflammatory diseases, where immunological mechanisms are known to play a major pathogenic role.