Metabolic clearance of insulin was measured, under circumstances of acutely and chronically altered endogenous plasma insulin, employing 1-131 bovine insulin (5 mc./mg., Abbott Laboratories) as tracer and the technic of constant infusion to equilibrium. Compared to normal subjects, clearance of radioiodinated insulin was unaffected by diabetes, was increased 25 per cent in obese subjects with hyperinsulinemia and did not change when their plasma insulin was reduced by seven days of fasting. Acute fourto fifteenfold elevation of endogenous insulin by glucose or tolbutamide injections to normal and obese subjects also failed to change clearance of radioiodinated insulin. These data support the assumption that alterations of plasma insulin in those circumstances largely reflect alterations in insulin secretion. However, in both normal and diabetic subjects, simultaneous clearances of unlabeled porcine insulin and radioiodinated insulin were also performed and disparate results obtained. Mean values were: unlabeled 861 ml./min. (Normals), 788 ml./min. (Diabetics) ; radioiodinated 227 ml./min. (Normals) ; 202 ml./min. (Diabetics). Ratio of unlabeled to radioiodinated clearance 3.8 (Normals), 4.1 (Diabetics). Because of this discrepancy, it is uncertain which clearance value affords the more accurate estimate of peripheral insulin delivery rate.