This study examined the interaction between hormones and serotonin-1A (5-HT1A) receptor modulation of prepulse inhibition (PPI) of the acoustic startle response. Male and female rats were gonadectomized; some castrated rats received testosterone- or estrogen-filled implants. Rats were randomly injected with saline or 0.02 or 0.50 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist. All rats showed a dose-dependent disruption of PPI in response to 8-OH-DPAT. In untreated castrated rats, this disruption was significantly reduced (33% compared with 78% in sham-operated rats). Testosterone treatment reversed this reduction, but estrogen was less effective. Ovariectomized and sham-operated rats showed similar PPI in response to 8-OH-DPAT. These data suggest that the effect of 8-OH-DPAT on PPI in male rats depends on circulating hormone levels, particularly testosterone.