The hormonal regulation of inositol 1-phosphate synthase (EC 5.5.1.4) in brain, liver and reproductive organs have been examined. In the hypophysectomized male rat the enzyme decreases in testis, epididymis, and liver and virtually disappears in the secondary sex organs. Thyroidectomy produces a large decrease in liver synthase only. Brain synthase is unresponsive to any hormonal change. Gonadotropins restore the activity to normal in the reproductive organs but not in the liver after hypophysectomy. In liver the activity is stimulated 30-fold by thyroid hormones in the hypophysectomized animal. We conclude that synthase of the reproductive organs is regulated more or less directly by the pituitary; liver synthase is regulated by the thyroid.