Seroquel (ICI 204,636) is a mixed D2/5HT2 antagonist with a preclinical profile suggestive of potential antipsychotic efficacy. We compared seroquel to clozapine in an animal model of sensorimotor gating deficits in shizophrenic patients. Like schizophrenic patients, rats treated with apomophrine (APO) exhibit deficits in prepulse inhibition (PPI) of acoustic startle. The ability of antipsychotics to restore PPI in APO-treated rats correlates (Rs = 0.991) with their clinical potency. Seroquel and clozapine both restore PPI in APO-treated rats. Seroquel's restoration of PPI in apomorphine-treated rats follows simple monotonic ascending dose-response properties, and is not accompanied by consistent changes in startle reflex amplitude. Seroquel's profile in this PPI model mimics that of other antipsychotics.