Measurements of fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations were made in 32 individuals—16 with normal glucose tolerance and 16 with non-insulin dependent diabetes mellitus (NIDDM)—further subdivided into two equal groups on the basis of body weight. In addition, endogenous glucose production was estimated in 32 subjects. Both fasting plasma glucose (251 ± 14 v 86 ± 1 mg/dL) and FFA (672 ± 35 v 434 ± 45 μEq/L) concentrations were significantly higher in patients with NIDDM (P < .001), and the differences between normal and diabetic existed in both weight groups. Rates of endogenous glucose production were also significantly elevated (P < .001) in diabetic (120 ± 6 mg/m² × min) as compared to normal subjects (73 ± 6 mg/m² × min), and these differences were also independent of degree of obesity. However, there were no significant differences between normal subjects and patients with NIDDM in either fasting or postprandial insulin concentrations. The similarity in insulin values for normal and diabetic subjects was true of both obesity groups, although insulin concentrations were somewhat higher in normal obese individuals as compared to their normal nonobese counterparts. Significant relationships were seen between values for fasting plasma glucose and endogenous glucose production (r = .89), fasting plasma glucose and fasting FFA (r = .64), and FFA levels and endogenous glucose production (r = .58) when all nonobese subjects were considered together. Essentially identical relationships, both qualitatively and quantitatively, were seen within the obese group. Thus, endogenous glucose production and plasma FFA concentrations are higher than normal in patients with NIDDM, and statistically significant relationships exist between plasma FFA concentration and both fasting plasma glucose concentration and endogenous glucose production.