A comparison has been made between the effect of a vitamin D—deficient diet and treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the morphology of chick epiphyseal cartilage and on the production of lactatein vitro by epiphyseal and articular cartilage. The cell populations in the growth plate were different following the two treatments. Vitamin D deficiency was characterized by an increase in proliferating cells, with a relative paucity of hypertrophic cells; EHDP treatment was characterized by an increase in hypertrophic cells. When similar cell types were compared, neither treatment changed lactate production from the control value. This stresses the need to correlate the morphology of cell types with their metabolic function. The present results indicate that the major effect of vitamin D deficiency in the chick is to block the differentiation of proliferating to hypertrophic cells. In contrast, EHDP may act by inhibiting calcification directly. Even though EHDP at the doses used is known to interfere with the production of 1,25-dihydroxycholecalciferol there is no block to cell differentiation under EHDP similar to that seen in dietary deficiency of vitamin D.