Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out.