The response of bone cells in organ culture to retinol and retinoic acid was studied. Both stimulated incorporation of [3H]thymidine into DNA by 16-day embryonic chick calvaria, but the time-course of the responses differed; the peak responses to retinol and retinoic acid occurred at about 18 h and 48 h, respectively. Although retinol inhibited chick bone collagen synthesis retinoic acid had no effect, but it did stimulate non-collagenous protein synthesis, whereas the effect on the latter of retinol was, if anything, inhibitory. When present with retinol, retinoic acid was able to attenuate the inhibitory effect of the former on chick bone collagen synthesis, but preincubation with retinoic acid had no such effect. In neonatal murine calvarial cultures, retinoic acid inhibited collagen synthesis selectively in the same manner as did retinol. The ability of chick osteoblasts to respond differently to retinol and retinoic acid suggests that both forms of the vitamin may have a role in bone formation and that their intracellular models of action may differ although the attenuation response indicates there may be some interaction between the two.