From the earliest days of the use of insulin in the treatment of diabetes mellitus there have been reports of cases in which larger doses were required than the clinical condition of the patient seemed to warant. Such cases were first described by Jaksch-Wartenhorst,1 Mahler and Pasterny,2 Umber and Rosenberg,3 Falta,4 Radoslav,5 Pollak,6 von Noorden and Isaac7 and Matthes.8 In the nine years since that time, numerous reports have revealed that in acidosis, in coma and in the presence of infection, hepatic disease or certain endocrine disorders the effectiveness of insulin may be decreased. Psychic disturbance and lack of exercise have been observed to raise the amount of insulin required. There are, however, many cases in which the poor response is unexplained. "Insulin resistance" as the term describing relative ineffectiveness of insulin is commonly used, although there is as yet no general agreement as to its definition. Joslin9 and