We investigated the possible existence of a negative short-loop feedback of circulating insulin on the parent beta cell in 10 lean Caucasians, 10 obese Caucasians, and 10 obese Pima Indians. Plasma insulin levels were raised acutely by 100 μU per milliliter for 90 minutes, and plasma glucose was maintained by the "clamp" technique. C-peptide levels were suppressed in all groups to approximately 50 per cent of basal values. However, the obese groups had absolute C-peptide levels much higher than those of the lean group. During the hour after infusion, the rate and magnitude of C-peptide recovery in the obese groups were higher than in the lean group. Thus, negative short-loop insulin-beta-cell feedback was operative in both the lean and obese states. Despite this suppression, the insulin-secretion rate in obese subjects was still greater than that in non-obese subjects. Inadequate feedback suppression may account in part for the prevailing hyperinsulinemia of the obese. (N Engl J Med. 1982; 306:1196–1202.)