The fear-potentiated startle paradigm is a valuable model for the investigation of the neuronal basis of fear. Previous studies have demonstrated that the neuropeptide corticotropin-releasing factor (CRF) plays an important role in fear-related processes, notably in the potentiation of the acoustic startle response. The present study investigated the role in fear-potentiated startle of CRF in the caudal pontine reticular nucleus, a brain nucleus that mediates the acoustic startle response. First, we showed that the central nucleus of the amygdala gives rise to a CRFergic projection to the caudal pontine reticular nucleus. In the second experiment, we iontophoretically applied CRF to caudal pontine reticular nucleus neurons and extracellularly recorded the activity of these neurons. CRF had a mainly excitatory effect on the tone-evoked activity of the neurons. In our third experiment, we injected the CRF antagonist alpha-helical CRF into the caudal pontine reticular nucleus of awake rats. Here, alpha-helical CRF dose-dependently blocked fear-potentiated startle, but had no effect on the baseline startle amplitude. The present results show that CRF-containing neurons which project from the central nucleus to the caudal pontine reticular nucleus are important for the enhancement of startle by fear, and further characterize the hypothetical neuronal circuitry underlying the expression of fear-potentiated startle.