The interactions of the antiemetic metopimazine (MPZ) and of the chemotherapeutic agents, cisplatin, carboplatin, doxorubicin, ctoposide and vincristine were investigated at five neurotransmitter receptor binding sites. MPZ had nanomolar affinity for α1, dopamine D2 and histamine H1 receptors, weak affinity for muscarinic cholinergic receptors, but no affinity for 5-hydroxytryptamine3 (5-HT3) receptors. Except for vincristine, which showed nanomolar affinity for muscarinic cholinergic receptors, none of the chemotherapeutic agents showed affinity for any of the receptors investigated at concentrations ranging between 10-5 and 10-7M. Accordingly, chemotherapy-induced nausea and vomiting seems to be mediated by mechanisms other than the direct interaction of cytostatics with the neurotransmitter receptors investigated. Our finding that MPZ is without affinity for 5-HT3 receptors and therefore seems to mediate its antiemetic effect predominantly by dopamine D2 receptor blockade makes it an interesting drug for use in combinations with the new class of antiemetics, the 5-HT3 receptor antagonists. Data obtained in a recent clinical trial support this observation.