Lower concentrations of immunoreactive (IR) β-endorphin were present in the neurointermediate pituitary lobes of streptozotocin-induced diabetic versus control animals at both 2 and 4 weeks after the onset of diabetes. The forms of β-endorphin-like material present appeared to be similar in both groups when studied with cation-exchange chromatography. Insulin therapy via minipump for 2 weeks did not alter this finding of lowered β-endorphin concentrations in diabetic animals, despite normalization of blood glucose levels and body weight gain. Lower IR β-endorphin levels were also found in neurointermediate lobes of weight-restricted rats, but this group had increased plasma IR β-endorphin concentrations compared to diabetic animals. Concentrations of IR β-endorphin in microdissected brain regions and in anterior pituitaries of the diabetic animals failed to show consistent changes; in addition, ACTH concentrations in pituitary lobes and plasma did not differ among groups. Circadian rhythmicity of plasma insulin and corticosterone concentrations was absent in the diabetic animals, although food and water intake, while elevated, showed the normal nocturnal pattern of increased ingestion. Furthermore, adrenal hypertrophy was present in the diabetic animals and was accompanied by an elevation of mean plasma corticosterone levels. The present findings indicate that diabetes is associated with a decrease of neurointermediate pituitary lobe synthesis of β-endorphin, while not affecting the processing of the peptide in this lobe, and confirm previous reports of altered adrenal function in diabetic a