CRF is recognised for its actions on pituitary ACTH release, but also has direct effects within the brain which are important in mediating physiological responses to stress. Behavioral effects of CRF include increased locomotor activity and inhibition of food intake and its actions on metabolism are mediated mainly by activation of the sympathetic nervous system. CRF appears to be important in the regulation of energy balance and body weight, influencing both food intake and sympathetically-mediated thermogenesis. A defect in the synthesis or release of CRF has been implicated in the development of obesity in laboratory animals, since the condition is alleviated by adrenalectomy, hypophysectomy or exogenous CRF treatment. Recent data have revealed an additional role for CRF as a mediator of the neuroendocrine and metabolic responses to immune signals, particularly cytokines. The central actions of CRF are independent of the pituitary but may involve release of proopiomelanocortin products within the brain. CRF is thus emerging as an important integrator of the physiological responses to stress, infection and immunity, a finding which may have important implications for future therapies.