The plasma insulin response to two successive stimulations by glucose was measured in 12 healthy subjects, 5 of whom demonstrated subnormal insulin responses to glucose infusion (low insulin responders). 15 g of glucose were injected rapidly i.v. at 0 and 20 min, and blood glucose and plasma insulin levels determined at intervals of 2-10 min. In both groups, the peak elevation of plasma insulin, and the peak insulinogenic index, were significantly inhibited at the second stimulation. The degree of inhibition was smaller in subjects with low insulin response. The integrated insulin response and the integrated insulinogenic index during the 20 min following glucose administration were also significantly inhibited at the second glucose challenge in subjects with low insulin responders. The degree of inhibition of the second insulin response (20-40 min) shows significant correlation with the insulinogenic index of the first response (0-20 min) in the total material. It is suggested that this inhibition of insulin release on repeating the stimulus, (a) may offer an explanation sustained stimulation by glucose; (b) is probably generated by the phenomenon of insulin secretion, and (c) might thus represent a negative feed-back loop in insulin secretion. (d) Decreased insulin secretion in low responders is not due to the presence of increased inhibition.