The documented ability of physical stress and cytokines to increase the secretion of corticotropin-releasing factor CRF by the paraventricular nucleus of the hypothalamus (PVN), coupled with our earlier demonstration that CRF acts within the brain to interfere with reproductive functions, led us to investigate the effect of lesions of the PVN on LH, testosterone, ACTH, and corticosterone (CORT) secretion. Bilateral lesions of the PVN were done electrolytically, and 2 weeks later a series of acute and chronic experiments were performed in intact or castrated male rats bearing indwelling jugular and/or intracerebroventricular cannulas. The first study involved a single 2-h exposure of intact male rats to footshocks (2 mA, 2-sec duration, 4 per min). Although PVN lesions did not measurably alter the ability of intermittent footshock to lower plasma testosterone levels, this treatment attenuated the rise in plasma ACTH and CORT. In a second study, which was done in castrated rats, shocks were delivered 2 h daily for 7 days, and circulating hormone levels were measured at the end of the last shock period. Plasma LH levels of stressed rats showed statistically comparable decreases in both sham- and PVN-lesioned animals. Chronic exposure to footshocks induced smaller increases of ACTH and CORT secretion in PVN-lesioned compared to sham-lesioned rats, but the lesions did not completely abolish stress-induced activation of the hypothalamic-pituitary adrenal (HPA) axis. The third experiment involved the central injection of the vehicle or 40 ng interleukin-1 beta (IL-1 beta) to castrated rats. As expected, IL-1 beta dramatically decreased plasma LH values and increased circulating ACTH and CORT levels measured 2 h later. Bilateral PVN lesion did not influence LH secretion after injection of the vehicle or IL-1 beta. In contrast, destruction of the PVN completely blocked the increase of HPA axis activity observed in sham-operated rats 2 h after the intracerebroventricular infusion of IL-1 beta. These results confirm our previous observation that exposure to either footshocks or interleukins alters the activity of the hypothalamic-pituitary gonadal and HPA axis. Additionally, the present studies suggest that the PVN, which represents the predominant hypothalamic nucleus controlling the response of the HPA axis to a number of stimuli, does not appear to be necessary for the antireproductive effects of intermittent footshock or immune activation.