The injection of protamine zinc insulin for the treatment of diabetes is followed in some patients by redness and swelling at the site of injection, sufficiently severe at times to lead them to discontinue the use of protamine zinc insulin. It therefore seemed desirable to investigate the nature of these reactions, especially from the standpoint of a possibly allergic mechanism. We here record our observations as to the causes and report a new observation, the induced sensitization to insulin which occasionally appears to follow the use of protamine zinc insulin. SENSITIVITY STUDIES The first part of this paper deals with the results of intracutaneous tests with protamine. The test material used was a solution of protamine in Coca's solution in a concentration containing 0.1 mg. of nitrogen per cubic centimeter. The tests were performed by the intracutaneous injection of 0.02 cc. of the test solution on the flexor surface of