Twelve antagonists of apomorphine-induced emesis in dogs were studied in different tests to evaluate their antiemetic specificity. Ten of these antagonists were neuroleptics: benzquinamide, clebopride, bromopride, prochlorperazine, haloperidol, chlorpromazine, thiethylperazine, metoclopramide, droperidol, and pimozide blocked conditioned responding in dogs and apomorphine-induced stereotyped behavior in rats. The use of these compounds as anti-emetics entails a risk of neurological side effects. Metopimazine and domperidone were devoid of neuroleptic activity. Metopimazine, however, showed potent alpha-adrenergic blocking activity, showed histamine H1 antagonism, and induced palpebral ptosis. Therapeutic doses of metopimazine are, therefore, likely to produce sedation and side-effects related to autonomic blockade, Domperidone showed potent antiemetic activity and, up to high doses, no other central or peripheral effects. Therefore, domperidone is the only specific antiemetic known.