The attenuation of the startle response termed "prepulse inhibition" (PPI) occurs when an abrupt startling stimulus is preceded 30-500 msec by a barely detectable prestimulus or "prepulse". PPI provides a measure of sensorimotor gating, which is a short time-constant central processing mechanism that is disrupted in patients with schizophrenia, and a number of other neuropsychiatric disorders. The present experiments examined normal PPI in the mouse, and assessed the effects of apomorphine, d-amphetamine, PCP, and MDMA on mouse PPI. As predicted, mice demonstrated robust and reliable PPI, and each compound tested disrupted PPI. As with rats, 2.0 mg/kg apomorphine, 10.0 mg/kg PCP, and 10.0 mg/kg MDMA disrupted PPI significantly, while 5.0 mg/kg d-amphetamine produced a large reduction of PPI that approached significance. Our findings suggest that the mouse may provide another model system for the study of sensorimotor gating mechanisms.