An investigation into the possible effect of thyroid stimulating immunoglobulin G on lipogenesis by adipocytes led to the discovery that all human IgGs exerted an insulin-like stimulatory effect on lipogenesis by rat adipocytes in vitro. Highly purified polyclonal IgGs prepared from normal subjects had stimulatory potencies similar to those of monoclonal IgGs obtained from patients with IgG myeloma. However, whole sera from myeloma patients with elevated IgG concentrations had a significantly higher stimulatory effect on adipocyte lipogenesis than control sera. These observations provide the first evidence that human IgG has an insulin-like metabolic effect, and that this effect is probably exerted by a nonspecific nonvariable portion of the IgG molecule. IgG may thus contribute to the non-suppressible insulin-like activity in the serum.