An insulin-stimulating protein was isolated from human plasma by a procedure involving Sephadex G-100 chromatography and reverse-phase HPLC. The isolated material gave a single band on SDS-polyacrylamide gel electrophoresis. This protein itself had no insulin-like activity, but enhanced fatty acid synthesis from glucose in rat adipose tissue explants in the presence of suboptimal concentrations of insulin. It also stimulated the effect of insulin on CO 2 liberation from glucose by isolated rat adipocytes and increased the maximal response to insulin.