We have investigated the effects of hyperglycemia in Type II diabetic patients on the somatostatin response to oral glucose. In these patients hyperglycemia prevailed (11.8 +/- 1.4 mmol/l) and was markedly increased to a maximum of 18.9 +/- 1.0 mmol/l following the ingestion of 75 g of glucose. The rise in blood glucose following glucose ingestion failed to induce a rise in plasma levels of somatostatin-like immunoreactivity. Biostator-regulated insulin infusion normalized fasting levels of blood glucose and reduced the hyperglycemia following glucose ingestion, i.e. blood glucose now rose from 4.6 +/- 0.1 to a maximum of 7.3 +/- 0.8 mmol/l. This moderate rise in blood glucose was accompanied by a significant (p less than 0.05) rise in somatostatin-like immunoreactivity. Somatostatin-28 and somatostatin-14 were separated using a Sephadex G-50 fine column. Biostator treatment suppressed plasma levels of both peptides during fasting conditions. Treatment was also accompanied by a rise in both peptides during the first hour following glucose ingestion; this rise did not occur in the untreated state. CONCLUSIONS lack of somatostatin response to glucose in non-insulin-dependent diabetes mellitus is associated with deranged metabolic control. Unresponsiveness to glucose entails the secretion of both somatostatin-28 and -14.