Somatostatin (SRIH) infusion has been widely used in metabolic studies of carbohydrate metabolism. While the effects of SRIH itself on various aspects of carbohydrate economy have been assessed in young adults, such studies have not been conducted in the elderly, which represent an increasingly important study group. To examine the effect of SRIH on insulin-mediated glucose disposal in the elderly, we studied 12 (7 men and 5 women) healthy nonobese subjects, aged 65-80 yr. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (22 mU/m2.min) or insulin with SRIH (250 micrograms/h) and glucagon (0.4 ng/kg.min) to maintain normal basal plasma glucagon levels. Basal plasma insulin, glucose, glucagon, GH, and glucose production and disappearance were similar on each occasion. Steady state (10-180 min) mean plasma insulin [insulin alone, 298 +/- 12 (+/- SE); insulin; glucagon, and SRIH, 304 +/- 15 pmol/L] and glucagon (insulin alone, 85 +/- 7; insulin, glucagon, and SRIH, 96 +/- 9 ng/L) concentrations were similar. At steady state (150-180 min) glucose production was suppressed to similar levels (insulin alone, 26 +/- 7; insulin, glucagon, and SRIH, 36 +/- 13 mumol/kg.min). However, steady state glucose disposal was significantly higher during the SRIH infusion (insulin alone, 295 +/- 26; insulin, glucagon, and SRIH, 346 +/- 32 mumol/kg.min; P less than 0.02). We conclude that SRIH augments insulin-mediated glucose disposal in healthy older subjects at physiological levels of insulin.