A B S T R A C T The erythropoietic effect of various thyroid hormones has been studied using erythroid colony formation by canine marrow cells. Although erythropoietin was required for colony growth, physiologic levels ofthyroid hormones significantly enhanced colony numbers. The order of potency of the thyroid compounds in their in vitro erythropoietic effect parallels their known calorigenic potency in vivo, suggesting that the in vitro effect is physiologically relevant. A series ofstudies linked the mechanism ofthyroid action to adrenergic receptors on responsive cells. Propranolol, a global ,8-blocker, inhibited thyroid hormoneresponsive erythroid colonies. When adrenergic antagonists having different blocking characteristics were added to culture, the thyroid hormone effect was blocked by those compounds having ,82-subspecificity.Velocity sedimentation analysis showed that the peak of colony-forming cells which respond to thyroid hormone and the adrenergic agonist, isoproterenol, sedimented at an identical rate (7.54 mm/h), which is slower than the major peak ofcolony-forming cells responding to erythropoietin alone (8.62 mm/h). These results demonstrate thyroid hormonal enhancement of in vitro erythroid colony growth which appears mediated by a receptor with (82-adrenergic properties.