The specific insulin binding systems developed with mono [12’Ilinsulin and purified plasma membranes of target cells [1, 2] provide a useful tool to study directly the insulin-receptor interaction in pathological states of altered sensitivity to insulin. The obese hyperglycemic (ob/ob) mouse represents a recessively inherited trait whose syndrome includes a marked resistance to both endogenous and exogenous insulin [3]. Simultaneously to the findings reported here, some of us [4] have@ served that liver membranes of ob/ob mice bind only 16-35% as much [12sI] insulin as membranes of the thin mice; control studies suggest that this alteration may be due, at least in part, to an impairment of the insulin receptor in the liver. We studied here the binding of [’25 Ilinsulin to fat cell purified plasma membranes of ob/ob mice. Under identical conditions of preparation and incubation, membranes of obese mice bound only 25% as much [’25 Ilinsulin as membranes of their non-obese littermates. Binding studies strongly suggest that affinity of membranes for insulin is identical or very close in both situations, whereas the insulin binding capacity of membranes of the obese animals is 4-7 times less than that of membranes of their thin littermates. It is as yet unclear whether this striking difference represents a primary defect or a secondary