The effects of streptozotocin-induced (STZ) diabetes on the response to immobilization stress were evaluated in adult male rats. Rats were injected with STZ or vehicle and handled daily to minimize stress. Four weeks later, half of the animals were lightly anesthetized with ether and immobilized for 20 min. At that time the stressed and nonstressed controls were sacrificed, and blood and tissue collected for hormone and amine determinations. Immobilization caused an increase in plasma glucose levels in the controls, but caused no further increase in the already high levels seen in the diabetic rats. Basal corticosterone levels did not differ between the STZ and control rats, and the increase after immobilization was of similar magnitude. The stress-induced increase in prolactin was attenuated in the diabetic rats. Immobilization caused a significant rise in plasma norepinephrine (NE) levels in control, but not in diabetic rats. Adrenal NE content and tyrosine hydroxylase activity were not significantly affected by stress or STZ treatment. Dopamine (DA) and NE content was increased in the hypothalamus of immobilized diabetic rats as compared to nondiabetic immobilized controls. These results demonstrate that diabetic rats respond to immobilization stress, but the endocrine and sympathetic nervous system response is impaired. Changes in the stress response may be related to changes in hypothalamic amine metabolism.