A comparison was made between the effects of anti-insulin receptor autoantibodies and normal human immunoglobulin G on the metabolic processes of isolated adipocytes. Anti-insulin receptor autoantibodies caused marked stimulation of glucose oxidation and glucose conversion to fatty acids, along with marked inhibition of lipolysis. Normal human immunoglobulin G, however, showed no metabolic effects on adipocytes. These observations indicate that only the anti-insulin receptor autoantibodies have an insulin-like metabolic effect. The present data thus suggest that the interaction of antibodies with adipocyte insulin receptors seems sufficient to produce the acute metabolic effects of insulin.