Histological studies were correlated with developmentally regulated isoenzyme transitions of creatine kinase (CK) in free soleus muscle grafts in mice, 1-25 days after operation. One series of muscles was treated with Marcaine, a myotoxin, in order to promote subsequent regeneration of the muscle. Another set of muscles was mock-treated. In both series of experiments, CK-BB and hybrid CK-MB isoenzymes reappeared transiently as the myoblasts fused and the muscle regenerated. CK isoenzyme transitions were somewhat more pronounced in Marcaine-treated muscle. Nine days after grafting the muscle, specific CK-MM was again present almost exclusively. In this regenerating system, therefore, isoenzyme transitions correlate with histologically detectable regenerative changes, recapitulating the events of embryonic muscle development.