We have studied (125I)-insulin binding and insulin dose response relationships of (14C)-methylglucose transport conversion of (14C)-glucose to CO2 and total lipids, and lipolysis at 37 degrees C and pH 7.4 in adipocytes from obese patients before (n = 15) and after fasting for 10 days (n = 6). Studies of adipocytes from obese before fasting showed a significant reduction of insulin binding when expressed to cell surface area and rightward shifts of the insulin dose response curves (decreased insulin sensitivity) for glucose transport, glucose oxidation, lipogenesis and antilipolysis. The decreased insulin sensitivity of adipocytes from obese was most likely the functional consequence of the impaired insulin binding. Moreover, decreased maximal glucose transport capacities were present in rat cells from obese both in the basal and maximally insulin stimulated states. Similarly, the percentage response above basal level to maximal insulin stimulation of glucose oxidation and lipogenesis was impaired to these cells. The latter findings suggest post receptor defects localized both to the transport system per se and to intracellular mechanisms involved in the metabolism of glucose. Conversely, the post receptor pathways for the insulin induced antilipolysis was intact in fat cells from obese man. Studies after fasting showed an increase of adipocyte insulin binding accompanied by an increased sensitivity to the antilipolytic effect of insulin with unchanged maximal responsiveness. However, due to marked post receptor alterations, the insulin stimulated glucose utilization was severely blunted. Thus, the glucose transport system of adipocytes from all fasted subjects was totally unresponsive to insulin, while some of the fasted patients had a slight response of glucose oxidation and lipogenesis in the presence of insulin in maximally effective concentrations.