Repeated restraint stress (3 hours of restraint on 3 consecutive days: RRS) in rodents produces temporary hypophagia, but a long-term down-regulation of body weight. The mild stress (MS) of an intraperitoneal injection of saline and housing in a novel room for 2 hours also inhibits food intake and weight gain, but the effects are smaller than for RRS. Previous exposure to RRS exaggerates hypophagia, glucocorticoid release and anxiety-type behavior caused by MS. Here we tested the involvement of brainstem corticotrophin releasing factor receptors (CRFR) in mediating energetic and glucocorticoid responses to RRS or MS and in promoting stress hyper-responsiveness in RRS rats. Administration of 1.3 nmol hCRF_(9-41), a non-specific CRFR antagonist, exaggerated hypophagia and weight loss in both RRS and MS rats, whereas 0.26 nmol had no effect in RRS or MS rats. In contrast, 2 nmol of the non-specific antagonist, astressin, had no effect on weight loss or hypersensitivity to subsequent MS in RRS rats, but blocked weight loss and inhibition of food intake caused by MS alone. MS rats infused with 3 nmol antisauvagine-30, a CRFR2 antagonist, did not lose weight in the 48 hours after MS, but 0.3 nmol did not prevent weight loss in MS rats. These data suggest that inhibition of food intake and weight loss induced by RRS or by MS involve different pathways, with hindbrain CRFR mediating the effect of MS on body weight and food intake. Hindbrain CRFR do not appear influence stress-induced corticosterone release in RRS rats.