The involvement of CRH and the sympatho-adrenal system in the effects of caffeine on food intake and body weight gain has been investigated in rats. Food intake and body weight gain were measured in male rats after the treatment with caffeine in combination with either an injection of the CRH antagonist alpha-helical CRH(9-41), a surgical adrenal demedullation (medullectomy), or a ganglionic blockade. Alpha-helical CRH(9-41) was injected in the lateral ventricle of the brain and hexamethonium was used to chemically block the ganglionic transmission. From 4 to 24 h following a caffeine injection, spontaneous food intake, which was cumulated from the time caffeine was injected, was significantly (p < 0.01) lower in caffeine- than in saline-treated rats. In food-deprived rats, the anorectic effect of caffeine was biphasic, being significant at 0.5 and 1 h after the caffeine administration, then vanishing for 3 h, and becoming significant again 6 h after the caffeine administration. In both the spontaneously fed and food-deprived rats, caffeine reduced the rate of weight gain, which was measured at the end of a 12- or a 24-h period following the caffeine injection. A significant (p < 0.05) interaction effect of caffeine and alpha-helical-CRH(9-41) was found on the cumulative food intake at 1, 6, and 8 h, and on the amount of food eaten between the 4-6-h interval following the injection of caffeine; the effects of caffeine on food intake and body weight gain seem largely prevented by the use of a CRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)