Serotonin (5-HT), its derivative 5-methoxy-tryptamine (MeOT) and ergot-alkaloid dihydroergosine (DHESN) suppressed the immune reaction of mouse spleen cells against sheep erythrocytes in vitro (PFC assay). Ketanserin and propranolol, antagonists of 5-HT, also caused suppression. However, cells incubated with propranolol 20 min before 5-HT or MeOT produced as many plaques as the non-treated cells. Preincubation with ketanserin resulted in similar interference, but the reversal was not complete. It is concluded that serotonin and related agents probably affect several types of immunocompetent cells participating in successive stages of the PFC reaction. The antagonists probably interfered via 5-HT receptors, adrenergic receptors or both. Immunosuppression observed with serotoninergic agents and their antagonists draws attention to possible side effects of such drugs.