Changes in activity of enzymes involved in energy metabolism have been determined in unfused, fused as well as in fusion-inhibited chick embryo muscle cells in vitro. Functionally related enzymes which supposedly are coded by "gene clusters" show a similar degree and rate of enzyme activity increase. Hexokinase and glucose-6-phosphate dehydrogenase reveal only slight activity changes during muscle cell development under the conditions studied. The elevation of phosphofructokinase can be distinguished from that of the other glycolytic enzymes by its higher rate of increase and from that of phosphorylase by its time-course of activity change. The Ca2+ dependence of the phosphorylase activity increase runs parallel to myoblast fusion rate. Experiments in which calcium was removed from cultures which had reached the final morphological state of mature myotubes 24 h after onset of fusion show that increases of enzyme activities are irreversible and that these increases proceed at unchanged rates. Experimental evidence suggest that although fusion and enzyme syntheses may be uncoupled, both are similarly triggered by being dependent on Ca2+ concentration.