Antihistaminic drugs of various chemical structure (chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, thenalidine) were tested on their action on the central serotonin system in mice. The test used was the antagonism to behavioral syndrome produced by D, L-5-hydroxytryptophan (5-HTP). Clemastine, promethazine and thenalidine inhibited 5-HTP-induced syndrome in doses of much lower than those inhibiting locomotor activity. Similar but weaker effect was produced by chlorcyclizine and diphenhydramine. It could be suggested that these compounds exert central antiserotonergic action. Chloropyramine and, more strongly, chlorpheniramine potentiated the action of 5-HTP; this may be due to the inhibition of serotonin uptake. Only mepyramine in these tests did not show any action on the central serotonin system.