To determine if improved control of plasma glucose in vivo affects insulin release from the perfused pancreas in vitro, genetically diabetic, nonobese Chinese hamsters were treated with insulin delivered via the 7-day Alzet minipump for 1 week (one minipump) or 4 weeks (four successive minipumps). Plasma and urine glucose levels fell during sc (minipump) infusion of varying dosages of insulin in roughly a dose-related manner. In hamsters with diabetes of recent onset (mean duration of glucosuria, 8 weeks) plasma and urine glucose levels decreased soon after the start of insulin infusion. There was a further progressive decrease throughout a 4-week period, and some animals died during the later weeks, apparently from hypoglycemia. The animals pancreases were then perfused in vitro with glucose. Mild diabetics (baseline plasma glucose levels, <200 mg<dl) which had been treated with saline solution showed a biphasic pattern of insulin release within the normal range, while insulin treatment sufficient to have caused hypoglycemia reduced both phases in vitro. More severe diabetics (baseline glucose, >200 mg>dl) showed significantly subnormal insulin release, while insulin treatment sufficient only to lower blood glucose levels into the normal range increased first phase release but did not affect the second phase. These studies suggest that improved control of blood glucose by continuous infusion of insulin can lead to improved endogenous insulin release, while dosages of insulin which cause hypoglycemia can suppress endogenous insulin release. © 1979 by The Endocrine Society.