In unanesthetlzed dogs, portal vein (PV) blood was repeatedly sampled by means of an indwelling cannual, simultaneously with blood from a superficial vein (SV), for determination of insulin by two-antibody immunoassay. Under control conditions, and in the postabsorptive state, mean serum insulin the SV was 31 [mu]U/ml, and the PV/SV ratio was about 2. Following intravenous Injection of 1 g of glucose/kg of body, serum insulin rose in 15 to 30 min. to peak values that were higher in the PV, and regressed to normal in 60 to 120 min. Growth hormone, 2 m/kg of body, injected dally for six to thirteen days, (1) increased PV and SV "fasting" serum insulin to the maximum of tenfold; the effect was found after one day of injection, was main?tained during injection, and returned to normal within four days of ceasing injection; (2) caused a further increase in serum insulin, in 100 min. following a meal, to a greater extent in the PV than in the SV-and (3) enhanced the rises in serum Insulin in PV and SV following intravenous injection of glucose, to maxima of nine- and sixfold, respec?tively; these rises were prolonged and the rates of regression of serum insulin from the peak values were reduced. Similar effects of growth hormone treatment were found in dogs under anesthesia at the time of glucose infusion. It is concluded that, during the treatment of several days, growth hormone caused continuously maintained increase in insulin secretion with enhanced secretion in response to a meal, and to the injection of a standard load of glucose. Further effects of growth hormone on serum wer (a) free fatty acid levels rose promptly, and remained above normal; (b) glucose tended to increase; (c) the insulin/ glucose ratio increased[long dash]the values were consistently greater in the PV than in the SV; and (d) in response to the glucose load, the rate of regression of serum glucose was reduced. The insulin/glucose ratio tended to remain stable at the particular "fasting" value, following glucose injection, both under the control conditions and during growth hormone treatment. This evidence indicates that growth hormone caused readjustment of the homeostatic control of the pancreatic Islets such that, at any particular level of glucose in the blood, Insulin was secreted at a higher rate.