Epidemiological studies have shown gender differences in the age of onset and symptoms of schizophrenia. Because sensorimotor gating mechanisms are deficient in schizophrenia, we studied the effect of administration of estrogen on prepulse inhibition of startle in rats, an animal model of sensorimotor gating. Rats were tested in an automated startle apparatus for their responses to random combinations of 115-dB sound pulses and prepulses of various intensity. Startle responses were reduced by increasing intensities of prepulses, indicating prepulse inhibition. Repeated administration of startle pulses caused gradual habituation of startle responses. Ovariectomy did not induce significant changes in either habituation of the startle response or prepulse inhibition of startle. Treatment with 17beta-estradiol caused an increase in percentage prepulse inhibition at all prepulse intensities at 18 h, but only at higher prepulse intensities at 30 min after injection. Habituation of startle responses was not affected. The enhancing effect of estradiol on prepulse inhibition was mimicked by testosterone, but not by dihydrotestosterone. Estradiol treatment increased prepulse inhibition similarly in controls or after disruption of prepulse inhibition induced by treatment with apomorphine or dizocilpine (MK-801). Our results may help to explain gender differences in schizophrenia and some of the beneficial clinical effects of estrogen treatment in this disease.