Experiments were performed to test the hypothesis that the rapid rises in plasma corticosteroid concentration which follow many varied stimuli are caused by a reset of the negative feedback control of plasma corticosteroid concentration to regulate at higher levels. An intravenous dose of histamine, which when given alone produced after 15 minutes an increment in plasma corticosterone concentration of 20 μg/100 ml., was injected 15–30 seconds after an intravenous dose of corticosterone (12 μg/100 gm. B.W.) selected to produce the same increment. The resulting increment in plasma corticosterone concentration equalled that produced by the corticosterone alone: the exogenous corticosterone completely prevented the increased secretion of corticosterone ordinarily provoked by histamine. In a similar fashion, doses of corticosterone (5, 12, and 35 μg/100 gm. B.W.) were selected to produce increments in plasma corticosterone concentration less (10 and 18 μg/100 ml.) and greater (39 μg/100 ml.) than that observed...