To elucidate the short-term effects of octreotide, a somatostatin analogue, on glucose tolerance in acromegaly, the plasma glucose and insulin responses to a 75-g oral glucose tolerance test (75-g OGTT) were examined in 6 patients. The glucose disposal rate (GDR) was also measured by the hyperinsulinemic euglycemic clamp method before and after the administration of octreotide. Before octreotide therapy, 2 patients had normal responses of plasma glucose and insulin to 75-g OGTT (normal glucose tolerance: NGT) and 4 showed hyperinsulinemia or glucose intolerance (glucose intolerance: GIT). GDR-insulin dose-response curves showed a normal pattern in patients with NGT and pattern of insulin resistance in patients with GIT. After 2-3 weeks of octreotide administration, plasma growth hormone (GH) levels decreased in all of the patients. The plasma glucose response to 75-g OGTT was not changed in any patient. In contrast, the plasma insulin response to 75-g OGTT was enhanced in patients with NGT but lessened in patients with CIT. Patients with NGT showed no significant change in GDR-insulin dose-response curves. Patients with GIT showed improvement in GDR at low levels of plasma insulin, but did not show complete improvement at high levels. These results indicate that octreotide improves insulin resistance at the insulin receptor site by lowering plasma levels of CH and insulin in acromegalic patients with glucose intolerance.