Both the neuropeptide, corticotropin-releasing factor (CRF) and the serotonin 1A (5-HT(1A)) receptor systems have been implicated in anxiety disorders and there is evidence that the two systems interact with each other to affect behavior. Both systems have individually been shown to affect prepulse inhibition (PPI) of the acoustic startle response. PPI is a form of sensorimotor gating that is reduced in patients with anxiety disorders including post-traumatic stress and panic disorder. Here, we examined whether the two systems interact or counteract each other to affect acoustic startle amplitude, PPI and habituation of the startle response. In experiment 1, Brown Norway (BN) and Wistar-Kyoto (WKY) rats were administered ether an intraperitoneal (IP) injection of saline or the 5-HT(1A) receptor agonist, 8-OH-DPAT 10Â min prior to receiving an intracerebroventricular (ICV) infusion of either saline or CRF (0.3Â Âµg). In a second experiment, rats were administered either an IP injection of saline or the 5-HT(1A) receptor antagonist, WAY 100,635 10Â min prior to receiving an ICV infusion of saline or CRF. Thirty min after the ICV infusion, the startle response and PPI were assessed. As we have previously shown, the dose of CRF used in these experiments reduced PPI in BN rats and had no effect on PPI in WKY rats. Administration of 8-OH-DPAT alone had no effect on PPI in either rat strain when the data from the two strains were examined separately. Administration of 8-OH-DPAT added to the effect of CRF in BN rats, and the combination of 8-OH-DPAT and CRF significantly reduced PPI in WKY rats. CRF alone had no effect on baseline startle amplitude in either rat strain, but CRF enhanced the 8-OH-DPAT-induced increase in startle in both strains. Administration of WAY 100,635 did not affect the CRF-induced change in PPI and there were no interactions between CRF and WAY 100,635 on baseline startle. The results suggest that activation of the 5-HT(1A) receptor can potentiate the effect of CRF on endophenotypes of anxiety disorders in animal models. This article is part of a Special Issue entitled 'Anxiety and Depression'.