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1) Hypophysectomy abolishes the diurnal rhythm of hepatic hydroxymethylglutarylCoA reductase activity in rats.2) A single dose of triiodothyronine applied to hypophysectomized rats restored the activity of the enzyme to the high control levels of sham-operated animals within 48 hours, but failed to do so within 6 hours.3) Injection of insulin into hypophysectomized rats failed to increase the low reductase activities. 4) The interrelationship of thyroid hormone and insulin in the regulation of hepatic cholesterol synthesis is discussed.