Abstract A polypeptide exhibiting diabetogenic and anti-insulin properties has been isolated from the urine of 33 of the 35 proteinuric diabetic patients. This material could not be found in the urine of 34 normal subjects and 32 diabetic patients without proteinuria. It was, however, detected chemically in one of seven nondiabetic patients with proteinuria, but the amount present was insufficient for biological testing. This polypeptide closely resembles, in physiochemical properties, that obtained from patients with lipoatrophic diabetes, as well as that isolated from the adenohypophyses of beef, sheep, and swine. The isoelectric point of the active polypeptide from all the above sources is approximately pH 4.1. In one diabetic subject who underwent hypophysectomy, this material disappeared from the urine following the operation. It is suggested that the source of the active principle isolated from the urine of diabetic patients with proteinuria is probably the pituitary gland.