We have previously shown that a significant inverse correlation exists between the height of the plasma insulin concentration and the efficiency of glucose uptake in the fasting state. Subsequently, we devised an infusion technic that provides a more specific measure of cellular resistance to insulin mediated glucose uptake. We have used this technic to study the relationship between fasting plasma insulin level and resistance to insulin mediated glucose uptake in twenty-two patients with normal oral glucose tolerance, fourteen patients with impaired glucose tolerance, and fourteen patients classified as having chemical diabetes mellitus. The results indicate a highly significant positive correlation between the degree of insulin resistance and fasting plasma insulin concentration (r = .69, p < .0001). A positive correlation (r = .43, p < .005) was also found between the degree of insulin resistance and the two hour plasma glucose level during an oral glucose tolerance test. However, no significant correlation was found between per cent adiposity and fasting insulin level, and the relationship between insulin resistance and fasting insulin level appeared to be independent of obesity or any other known cause of decreased insulin responsiveness. These studies indicate that: (1) increases in fasting insulin levels and increase in resistance to insulin mediated glucose uptake are closely related, and that these changes can occur in the absence of any of the “known” causes of decreased insulin responsiveness; (2) in the types of subjects we have studied, deterioration of glucose tolerance is closely related to increases in insulin resistance; and (3) the increases in fasting insulin levels which we have observed appear to be compensatory attempts to overcome the resistance to glucose uptake.