The effect of oral administration of vanadate on the transport and hydrolytic components of the glucose-6-phosphatase system in liver homogenates from streptozotocin-induced diabetic rats was examined. Blood glucose was normalized in diabetic rats receiving 0.8 mg/ml vanadate but a catabolic effect was observed on body and liver weight. Significant changes in the coupled reactions for glucose-6-phosphate transport by T1 and hydrolysis by the enzyme were noted. The dramatic elevation in the maximal velocity of glucose-6-phosphatase brought about by diabetes was suppressed by vanadate administration. As a result, the relationship between T1 and the enzyme returned to the normal range. It is concluded that the suppression of glucose-6-phosphate hydrolysis in diabetes may contribute to the normalizing effect of vanadate on blood glucose.