Insulin resistance was estimated in fifty nonobese subjects who were classified as normal (thirty subjects) or as having chemical diabetes (twenty subjects) on the basis of a standard oral glucose tolerance test. Insulin resistance was determined by administering a constant intravenous infusion of epinephrine, propranolol, glucose and exogenous insulin to each subject for 150 minutes and by measuring the resultant steady state plasma glucose levels attained during the last sixty minutes. Under these conditions, endogenous insulin secretion and hepatic glucose output are suppressed, and similar steady state plasma levels of the exogenously infused insulin are achieved in all subjects. Since all patients are challenged with comparable glucose loads, the height of the steady state plasma glucose response becomes a direct measure of an individual's resistance to insulin-mediated glucose uptake. With this approach we found that the mean (± S.E.) steady state plasma glucose level in patients with chemical diabetes was 224 ± 15 mg. per 100 ml. as compared to 126 ± 12 mg. per 100 ml. in control subjects. This difference was statistically significant (p <.001) and could not be attributed to differences in degree of obesity between the two groups. Furthermore, when individual values were examined it was apparent that relatively little overlap existed between steady state plasma glucose levels in normal and diabetic subjects. These results indicate that resistance to insulin-mediated glucose uptake is a characteristic of nonobese patients with chemical diabetes.