The effects of DL-alpha-difluoromethylornithine (DFMeOrn), an irreversible inhibitor of L-ornithine decarboxylase, on immunoglobulin production were studied in vitro using human peripheral blood lymphocytes stimulated with pokeweed mitogen. DFMeOrn inhibits in a concentration-dependent manner the usual pokeweed mitogen-induced increases of polyamine contents (putrescine, spermidine, spermine) and of [3H]thymidine incorporation. In parallel with the reduction of polyamine content and of thymidine incorporation, IgG and IgM productions are diminished, a 70% decrease being observed at 5 mM DFMeOrn concentration. Therefore, it appears that inhibition of polyamine biosynthesis may ultimately interfere with the cellular immunologic response by blocking cell proliferation. These findings certainly deserve further consideration both under in vitro and in vivo conditions.