Our understanding of the molecular basis of insulin actin remains incomplete, but important new insights have been achieved recently. All available evidence to date indicates that intracellular signalling by the hormone results from its initial interaction with specific cell surface receptors. Insulin receptors from all tissues studied to date appear to be minimally composed of two Mr 125,000 subunits denoted as alpha and two Mr 90,000 subunits denoted as beta. The beta subunit is extremely sensitive to proteolytic cleavage near the center of its amino acid chain. The four subunits are linked together by disulfide bonds to give a symmetrical configuration with a stoichiometry of (alpha-s-s-beta)-s-s-(alpha-s-s-beta). This structure is remarkably similar to the general subunit composition of immunoglobulin G molecules and provides a structural basis for the postulate that this minimum insulin receptor structure may be divalent for binding hormone. A second area of recent progress involves the successful generation of a soluble factor or factors by insulin that are capable of modulating the activity of insulin-sensitive enzymes such as pyruvate dehydrogenase, glycogen synthase and cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase in cell-free systems. Indirect evidence indicates that the putative mediator or mediators of insulin action exhibits properties expected of a low molecular weight peptide, including destruction by proteases. The data available are consistent with the hypothesis that insulin-receptor interaction leads to the activation of a membrane protease that catalyzes the release of a peptide mediator or mediators of insulin action.