By total pancreatectomy 41 dogs were made diabetic. Of these, 15 dogs remained untreated, served as diabetic controls, and died within x = 7 +/- 1 days postoperatively. In the experimental groups the best results were obtained (as judged by K values of iv glucose tolerance test and iv Tolbutamide test curves) after 20 min of incubation with collagenase and immediate transplantation into the splenic pulp. After 15 min and 25 min of incubation, normoglycemia regularly occurred, but in the 20 min collagenase group the K values resembled most closely those of normal dogs. The animals stayed normoglycemic and were observed for up to 6 months. Splenectomy led to reocurrence of the diabetic state and death within 4.8 +/- 1.5 (S.E.) days.