The insulin and glucagon responses to 10 mM glucose and 10 mM arginine were studied in pancreata isolated from nondiabetic diabetes-prone and diabetes-resistant BB/W rats at 60, 80, and 140 days of age and in diabetic BB/W rats on the 1st and 14th days of their diabetes. In the former group the insulin response to glucose declined progressively with age (r = -0.575; P less than 0.01) and at 140 days was significantly below age-matched diabetes-resistant controls (P less than 0.05). The insulin response to arginine did not decline with age in either group. For diabetic rats, on the first day of the diabetes, the insulin response to glucose was absent but the response to arginine did not differ from nondiabetic controls. On day 14 responses to glucose and arginine were both absent. The glucagon response to arginine showed no trend despite a decline in baseline glucagon secretion. Endocrine tissue in nondiabetic diabetes-prone rats made up 0.8 +/- 0.2% of the pancreas at 60 days of age and 0.52 +/- 0.22% at 140 days of age; the latter was significantly less than in 140-day-old diabetes-resistant controls (P less than 0.05). In diabetic rats on the 1st and 14th days of diabetes endocrine tissue was 0.2 +/- 0.1% and 0.07 +/- 0.02%, respectively. The glucose transport rate in islets isolated on the first day of diabetes was profoundly reduced compared to age-matched nondiabetic diabetes-prone controls. Thus, a population of arginine-responsive, glucose-unresponsive islets with low glucose transport rates is present at the onset of overt diabetes in BB/W rats.