Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity in childhood. When these five patients were separated from the original 14 obese patients, enhanced differences in insulin binding to adipocytes were observed when normals and the remaining 9 obese subjects were compared. Similar findings were obtained with isolated circulating mononuclear cells from these same patients. Presumably the five normoinsulinemic obese patients were not insulin-resistant, and, thus, the data indicate that insulin binding to adipocytes was decreased only in insulin-resistant obese patients. This conclusion was strengthened by finding a highly significant correlation (r=-0.71, p less than 0.001) between insulin binding to adipocytes and fasting plasma insulin level, while a weaker correlation (r=-0.49,p less than 0.01) existed between insulin binding and degree of obesity. Finally, when insulin binding to adipocytes and mononuclear cells from the same individual was compared, a significant positive correlation was found (r=0.53,p less than 0.01). CONCLUSIONS (a) insulin binding to adipocytes and mononuclear cells is decreased in cells from insulin-resistant obese patients; (b) a significant inverse relationship exists between fasting plasma insulin level and insulin binding to adipocytes; and (c) in obesity, events that affect insulin receptors on adipocytes similarly affect insulin receptors on mononuclear cells.