The possibility that somatostatin has a direct inhibitory effect on intestinal D-glucose absorption was studied in rats using intact intestinal loops and everted jejunal segments. Somatostatin infusion in vivo produced a significant fall in plasma glucose concentration (P less than 0.001) and a fall in pooled plasma insulin concentration to 51% of control values. However, somatostatin infusion did not alter significantly from control values the rate of glucose disappearance from the perfused jejunal lumen in vivo or the appearance of gut-derived plasma glucose. The lack of an inhibitory effect of somatostatin on glucose absorption in vivo was confirmed using two in vitro studies. When increasing concentrations of somatostatin (0-10(4) ng/ml-1) were added to both mucosal and serosal solutions, no significant differences were seen for net transmural flux or unidirectional flux of D-glucose in everted jejunal segments. These studies suggest that somatostatin in the rat does not influence plasma glucose concentration by inhibiting intestinal glucose transport at physiological concentrations of glucose and over a wide range of somatostatin concentrations.