Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). PPI provides a simple operational measure of sensorimotor gating, serving to prevent the interruption of ongoing perceptual and early sensory analysis. In accord with postulated deficits in early stages of information processing, there is ample evidence that PPI is disrupted in individuals with schizophrenia. PPI in animals is thought to represent a well-validated model for evaluating potential new treatments for schizophrenia. Currently, available data on the differential effects of typical and atypical antipsychotics suggest that atypical antipsychotics, in particular clozapine and risperidone, may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, studies have so far used small samples and/or between-subjects designs, and not examined the effects of other concomitant medications that may also influence PPI. The directions are identified for further applications of this model using within-subjects longitudinal designs and reasonable sample sizes to establish superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in schizophrenic populations.