The in vivo and in vitro growth hormone (GH) responsiveness to growth hormone-releasing factor [rGRF(l-29)NH2] was evaluated in a dietary obese rat model. Sprague-Dawley rats were divided into two groups after weaning. The control group received a semisynthetic defined diet, and the cafeteria-fed group was maintained on a mixed energy-rich palatable diet. After 2 months of diet, the cafeteria-fed rats were divided into two groups, according to their degree of weight gain compared to controls: group I: 0%; group II: 24%. After 5 months of diet, the weight increase was, respectively, in groups I and II, 12 and 41%, as compared to controls. Under pentobarbital anesthesia, rGRF(l-29)NH2 was injected intravenously in two consecutive doses of 0.8 and 4.0 µg/kg body weight into the control and cafeteria-fed rats. After 2 months of diet, a significant decrease of basal GH levels and GH peak response to the 4.0 µg/kg rGRF dose was observed in both cafeteria-fed rat groups as compared to the control group. After 5 months of diet, basal GH levels decreased in both cafeteria-fed groups. However, a significantly blunted GH response to both doses of rGRF occurred only in group II. After 5 months of diet, perifused anterior pituitary cells of control and cafeteria-fed rats were challenged with increasing concentrations of rGRF (6.25, 25 and 100 pM). The basal GH secretion was similar in all groups but the stimulated GH release in response to 25 and 100 pM GRF, expressed as peak value, was depressed in group II, compared to controls. Epididymal fat pad weights were significantly increased in group II 5-month-old rats, compared to controls (p < 0.05). A positive linear correlation was found between fat pad weight and body weight (r = 0.68, p < 0.01). In addition, the peak GH response to 4.0 µg/kg body weight of rGRF was inversely correlated with the total body weight (r = –0.57, p < 0.05) and the fat pad weight (r = –0.71 p < 0.02) in all the cafeteria-fed rats. These data demonstrate an in vivo decreased basal and stimulated GH response to rGRF and an alteration of the GH-stimulated release at the pituitary level in an obese cafeteria rat model and suggest that obesity and/or a cafeteria diet blunts the GH response.