There are many candidate mechanisms to explain the phenomenon of delayed microvascular disease in the diabetic. All may play some part in determining the genesis, the evolution or the ultimate degree and form of the angiopathy. General metabolic and humoral factors may provide the pathogenetic background against which special local conditions, e.g., in the retina or renal cortex, will determine the morphology of the angiopathy and its functional and structural consequences. Some of the processes occurring in the diabetic person may, however, be of major importance in initiating and maintaining conditions for the evolution of microvascular disease. The hemodynamic changes and the vascular responses to them that we have described are, we suggest, very likely to be an important component of this sort. Unlike the later structural changes, these hemodynamic phenomena are to be found very early in the diabetic state. Of most clinical importance, perhaps, is that they appear, with the achievement of adequate metabolic correction, to be reversible.