We have described a technique for quantifying skeletal muscle metabolism in man in. situ by measing blood flow through the forearm and appropriate arteriovenous differences in concentration of selected metabolites ( 1 ). The technique lends itself to analysis of local effects of hormones and other possibly potent agents. The agent can be injected into the brachial artery at constant rate with the solution of Evans blue dye used to measure blood flow. The quantity of the agent injected can be sufficiently large to exert a measurable effect in the forearm but sufficiently small so that, upon approximately 100-fold dilution when forearm venous effluent mixes with blood in the heart and great vessels, there is no measurable systemic effect. There are, therefore, no detectable systemic counter-regulatory processes set in motion by the agent to complicate the primary response of the forearm to the agent itself.It is the purpose of this report to describe the effects on forearm muscle metabolism of insulin administered in this fashion. We sought information concerning the following two problems. 1) Only a minor fraction of oxygen consumed by forearm muscle at rest can be accounted for by dissimilation of glucose abstracted from arterial blood (1). Is this because resting muscle is so poorly permeable to glucose? If glucose uptake is increased, say by exhibition of insulin, is oxidation of glucose enhanced necessarily?2) Do the temporal and molar relations between glucose uptake and potassium uptake by muscle in response to insulin suggest that insulin-induced * These studies were aided by Contract Nonr-248 (34) potassium movement is or is not secondary to the effect of insulin on glucose? METHODS Net uptake (or output) of a metabolite by forearm tissues was calculated by the equation 0 = F(A-V), where 0 is uptake (or output) of the metabolite in units of mass per minute per 100 ml of forearm, F is blood (or plasma) flow through the forearm in units of ml per minute per 100 ml of forearm, and A and V are concentrations of the metabolite in arterial and in venous blood (or plasma), respectively, in units of mass per milliliter. The technique was as described previously (1). Briefly, a double-lumen needle was inserted into the brachial artery. A polyethylene catheter was threaded into an antecubital vein and passed distally and deeply so that it sampled blood draining muscle but also, undoubtedly, adipose tissue interspersed among muscle. A second catheter was threaded into a more superficial vein, sampling mainly from skin and subcutaneous adipose tissue. Blood flow was measured by the indicator-dilution method in which Evans blue dye was injected continuously at constant rate into the brachial artery (2).Ten young adult subjects, 6 men and 4 women, were studied. All were medical students or laboratory personnel in good health and near ideal body weight. Dietary history of carbohydrate intake was normal. No food was taken after 7 p.m. on the evening preceding the experiment. The first blood samples were obtained betwee...