Somatostatin and somatostatin analogues are inhibitors of insulin, glucagon, and growth hormone secretion. However, it has not been determined whether it is somatostatin or its analogues which affect these hormones when used concomitantly. The effect of the somatostatin analogue SMS 201-995 on exogenously infused insulin was observed in ten healthy volunteers. The study was carried out on two occasions with at least a 1-week interval. Each subject was infused with saline throughout the study and insulin at a rate of 40 mU/kg per hour between 60-160 min of the study (step A) or SMS 201-995 in a 75 micrograms IV bolus following at a rate of 75 micrograms/h for 160 min and insulin at the same rate and duration (step B). Hyper-insulinemia and SMS 201-995 significantly suppressed C-peptide secretion, but the degree of C-peptide suppression was greater in the SMS 201-995 infused step than in the insulin-only infused step. Blood glucose levels decreased markedly throughout the infusion of insulin with or without SMS 201-995. In step B, the decrease in blood glucose was greater than in step A. Insulin levels in step B increased to higher levels than in step A (from 81.1 +/- 7.7 to 363.9 +/- 22.7 mmol/l and from 82.7 +/- 8.6 to 229.0 +/- 23.4 mmol/l, respectively). These results show that SMS 201-995 increases the level of exogenously infused insulin. This is probably due to the impaired clearance of exogenous insulin.