The saturable insulin binding is linked to insulin degradation in two important target cells: The hepatocyte and the adipocyte. One of the consequences is that the changes in binding which are observed under various conditions cannot a priori be regarded as caused by either increased number of receptors or increased affinity of the binding site. This observation raises new questions. For instance, could the effect of insulin be mediated by a fragment of the molecule? No evidence which is available for the moment seems to rule out this hypothesis. The findings with insulin analogues, the kinetics of insulin binding and activation and the effect of mild trypsin treatment, would equally well support the hypothesis that the binding itself causes activation of hexose transport and that degradation secondary to binding mediates the activation.