We examined the release of growth hormone-release inhibiting factor (somatostatin) from dispersed hypothalamic cells obtained from mature diabetic rodents and normal age-matched controls, in an attempt to demonstrate a possible hypothalamic defect which might underlie some of the reported abnormalities in somatotrophic function in diabetes mellitus. Insulinopoenic diabetes was induced by either streptozotocin or alloxan. Somatostatin release from cells from diabetic rats was diminished both basally and after stimulation by membrane depolarisation. Stimulated release was calcium dependent in cells from both normal and diabetic animals. The defect was present in both streptozotocin and alloxan induced diabetes. We also compared hypothalamic somatostatin release from cells obtained from obese hyperinsulinaemic C57 BL/Ks db/db diabetic mice and non diabetic lean litter mates (db/-). Despite longstanding marked hyperglycaemia, no significant alteration in somatostatin release was apparent. Likewise, starvation of rats for 5 days did not result in significant diminution of somatostatin release. These observations document a defect in hypothalamic somatostatin release in experimentally induced insulinopoenic diabetes, which is not apparent in the db/db mouse, suggesting that glucose per se is not responsible. Rather than the anticipated increase in hypothalamic somatostatin release in insulinopoenic diabetes, a reduction in release was observed. These observations are compatible with the hypothesis that increased hypothalamic somatostatin release is not responsible for abnormal growth hormone secretion in this model.