We tested risperidone and ritanserin, serotonin-S2 receptor antagonists, for their effects on in vitro polyclonal IgG and IgM synthesis by human peripheral blood mononuclear cells (PBMC) stimulated with pokeweed mitogen (PWM). On the basis of the previously reported effect on immune function in vivo risperidone in this study was tested in three different groups of PBMC: healthy donors as well as schizophrenic patients before risperidone treatment and schizophrenic patients after the treatment with risperidone. IgG and IgM production after 7 days of culture was measured by ELISA. Risperidone decreased IgG synthesis (p<0.05) in PBMC of healthy subjects only at the highest concentration (10~6 M) and IgG synthesis enhanced by 5-HT was antagonized by risperidone. This effect, however, was not statistically significant. Neither risperidone nor ritanserin, in the concentration range 10-8- 10~6M, affected IgM synthesis in this group. Risperidone did not affect the production of IgG and IgM by PBMC of schizophrenic subjects in PWM-stimulated cultures both before and after risperidone therapy. The spontaneous production of IgG in PBMC of schizophrenic subjects before therapy was decreased (p<0.05) at concentrations 10-6-10~7 M of risperidone. We conclude that risperidone and ritanserin did not increase polyclonal IgG and IgM synthesis in vitro in contrast to neuroleptics currently used in clinical practice.