IT has been recorded by several workers that insulin, though effective in most diabetics in lowering the blood-sugar level to normal, in a small fraction of cases either does not react at all or very high doses are required for beneficial results. Rosenthal1 observed that one of his patients showed no relief in hyperglycaemia even by daily injections of 100–120 units of insulin. Isolation of inactive insulin has been reported by Bhima Rao et al.2, and Himsworth3 reports on diabetics insensible to insulin. Joslin4 regards adiposity as a precursor of diabetes and this idea has recently been supported by our evidence5 that disturbance in the intermediary metabolism of fat is one of the factors responsible for the onset of hyperglycaemia. It has also been observed that hyperglycaemia caused by repeated injections of pyruvic acid, aceto-acetic ester, and -hydroxy butyric acid, etc., is followed by a rapid fall in blood-sugar level, thus suggesting the possibility of extra stimulation of islet cells. This is to be expected when there is a chance that the internal insulin may be destroyed or inactivated by such substances when administered to the system.