AbstractInduction of the transglutaminase activity of a transformed mouse epidermal cell line (PAM 212 cells) by 1α,25‐dihydroxyvitamin D3(1α,25‐(OH)2‐D3), the active form of vitamin D3, was investigated. Addition of 1α,25‐(OH)2‐D3to a culture medium stimulated twice the transglutaminase activity at a concentration of 10−7M, but vitamin D3, prostaglandin E1, E2, and F2afailed to show this induction. Phorbol 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA) and ***dexamethasone also induced an increase in transglutaminase activity. Exposure to both 1α,25‐(OH)2‐D3and retinoic acid caused remarkably synergistic effects on the induction of transglutaminase in the PAM 212 cells. In contrast, simultaneous addition of 1α,25‐(OH)2‐D3and TPA was antagonistic and resulted in less than additive induction. Vitamin D3also showed a similar but lesser effect. These results suggest that 1α,25‐(OH)2‐D3induces the transglutaminase activityviamechanisms disparate from those of retinoic acid a