The synthesis of collagen under conditions in which polypeptide chain initiation is selectively inhibited by medium hypertonicity was compared to the synthesis of other proteins in chick embryo leg bone cells in monolayer cultures. Three different approaches showed that collagen synthesis is far more sensitive than the majority of other cellular proteins to the hypertonic initiation block. In marked contrast, the synthesis of an unidentified protein, migrating with an apparent molecular of 45,000 to 50,000 is particularly resistant to hypertonicity. The effects of hypertonic conditions were found to be readily reversible upon restoration of isotonicity. Since these suboptimal growth conditions can decrease the amount of collagen synthesized relative to total protein synthesis, they provide an experimental model for the study of the translational control of the synthesis of collagen and other proteins.