This report analyzes the in vitro characteristics of ¹²⁵I-insulin binding to the monocytes of nine patients with the syndromes of acanthosis nigricans and insulin resistance. The 3 Type A patients (without demonstrable autoantibodies to the insulin receptor) had decreased binding of insulin due to a decreased concentration of receptors. In these patients the residual receptors demonstrated normal dissociation kinetics, negative cooperativity, and were blocked by anti-receptor antibodies in a manner similar to normal cells. In contrast, monocytes from the 6 Type B patients (with circulating anti-receptor autoantibodies) had decreased binding of insulin due to a decrease in receptor affinity. Insulin binding to monocytes of Type B patients demonstrated accelerated rates of dissociation with no evidence of cooperative interactions among insulin receptors. When coupled with previous data, the present studies further suggest that different mechanisms account for the defects in insulin binding and insulin resistance observed in these patients.