Published models of mammalian whole-body glucose metabolism generally assume that glucose uptake is proportional to circulating glucose concentration at constant insulin concentration. One widely used model labels the increased whole-body glucose uptake seen with increased venous glucose concentration as "glucose effectiveness." In 1956 and 1957, we found on average no change in forearm glucose uptake when we doubled, or more than doubled, local forearm arterial glucose concentration by close arterial infusion so that pancreatic arterial glucose concentration did not change. These experiments are being reported in extenso for the first time. Since that time, two other groups have found in glucose/insulin clamp experiments that whole-body glucose uptake was not proportional to hyperglycemic concentrations, although uptake did increase. It was hypothesized that perhaps some organs and tissues do increase uptake proportionally and other tissues not at all. Our results show that skeletal muscle is a tissue in which glucose uptake, at constant insulin, is not changed acutely by hyperglycemia; there is no forearm glucose effectiveness. We suppose that this constancy occurs because there are so few GLUTs on the sarcolemma surface in the basal state and that they are saturated even at euglycemia. We also report earlier experiments from 1954 to 1955 in which comparable hyperglycemia was reached by a large oral dose of glucose, with a 10-fold increase in glucose uptake. The arterial glucose time curve during hyperglycemia was 20-30 mg/dl higher than the forearm venous curve.