We have studied the responses of insulin and somatostatin to glucose and arginine in the perfused pancreas of GK rats, which spontaneously develop mild noninsulin-dependent diabetes without concomitant obesity. Our GK rats have been obtained after at least 42 generations of inbreeding of Wistar rats with initial selection for increased blood glucose levels during glucose tolerance tests. During perfusion with a high (16.7 mmol l-1) glucose concentration, normal responses of insulin and somatostatin were found in pancreata from non-diabetic control rats. In GK pancreata, however, these responses were virtually abolished. When the glucose concentration of the perfusion medium was switched from 16.7 to 3.3 mmol l-1 glucose, a transient increase- 'off-response' -in both insulin and somatostatin secretion was noted in GK but not in control pancreata. During the subsequent stimulation with arginine (20 mmol l-1), insulin and somatostatin responses were similar in pancreata from non-diabetic and GK rats. The pancreatic content of insulin did not differ between non-diabetic and GK rats, whereas the content of somatostatin was increased by 56% (P < 0.025) in GK glands. In conclusion, abnormalities assigned to pancreatic hormone secretion in the GK rat comprise not only markedly impaired insulin but also somatostatin response to glucose. Since there was no decrease in pancreatic content of these hormones in GK rats, the cause of glucose insensitivity of the hormone-producing cells is likely to reside in a defective stimulus-secretion coupling rather than decreased availability of the hormones.