Infants of diabetic mothers have an increased risk for thrombosis. The etiology of their hypercoagulable state is unknown. To examine the effects of hyperinsulinemia on the development of coagulation during fetal life, 10 sets of chronically catheterized fetal lambs were studied. One twin from each pair of 120-d gestation lamb fetuses was infused with insulin at a rate of 2.5 U/h for 48 h, whereas its twin sibling was infused with an equal volume (20 ml.) of dextrose 5% in water Changes in coagulation factor activities were measured before and after the infusions, and differences were analyzed by pairedttests. There was a significant decrease in protein C after insulin treatment in the insulin-treated twins. There were relative increases in fibrinogen factors V, VII, and XI when the insulin-treated group was compared with the controls. The changes are consistent with an increased risk of thrombosis and may explain, in part, the higher incidence of thrombosis in infants of diabetic mothers.