In the present study we have examined the effect of clozapine, an atypical antipsychotic drug, on latent inhibition (LI) using the conditioned emotional response (CER) procedure. In this procedure, ten pre-exposures to the to-be-conditioned stimulus result in weak or no LI whereas 30 pre-exposures produce robust LI. Three different experimental protocols were used to study the effects of clozapine: facilitation of LI in animals subjected to ten pre-exposures to the to-be-conditioned stimulus; antagonism of the disruptive effect of amphetamine (1 mg/kg, s.,c.) on LI in animals receiving 30 pre-exposures; antagonism of the disruptive effect of nicotine (0.6 mg/kg, s.c.) on LI in animals receiving 30 pre-exposures. High doses of clozapine (3 and 10 mg/kg, s.c.) disrupted the CER in non pre-exposed animals. Despite this, clozapine significantly facilitated the development of LI at 1 and 10 mg/kg and significantly attenuated the disruptive effects of nicotine at 0.3 and 1 mg/kg and of amphetamine at 2 and 5 mg/kg. These results demonstrate that clozapine is active in the LI model and further support the utility of this model in the study of mechanisms of action of antipsychotic drugs.