The BB rat is the experimental analogue of human juvenile diabetes mellitus. From 30 through 120 days after birth, 59 BB rats were treated with water (n = 20), or FK 506 in daily intragastric doses of 1 mg/kg (n = 19) or 2 mg/kg (n = 20). Diabetes developed in 75%, 15%, and 0% of the three groups. Animals protected from diabetes by FK 506, and killed in the nondiabetic state at 120 days had normal intraperitoneal glucose tolerance tests, virtual absence histopathologically of autoimmune insulitis, normal pancreatic insulin content, and immunocytochemical confirmation of islet insulin and glucagon content. Forty five to 75 days after stopping FK 506, about 3/4 of the animals who were diabetes free at 120 days have remained so. These results provide support for a clinical trial of FK 506 for recent onset diabetes.