Denervation of the gastrocnemius muscle at various stages of development reduces muscle weight and creatine kinase activity. An inverse relationship between the muscle-specific enzyme, creatine kinase, and the lysosomal enzyme, acid phosphatase, was shown. An increased percentage of the BB isoenzyme of creatine kinase is observed after long-term denervation. Apparently the muscle tissue has the ability to regenerate and presumptive myoblasts are formed from satellite cells. When the denervated muscle is treated with dibutyryl-cyclic-GMP a less decreased muscle weight is found. The total creatine kinase activity per muscle has increased which means that after dibutyryl-cyclic-GMP administration new muscle tissue has been formed. Similar effects could not be demonstrated with either cyclic AMP or succinylcholine. The higher percentage of the BB isoenzyme after dibutyryl-cyclic-GMP administration supports the theory that presumptive myoblasts are derived from satellite cells. Succinylcholine also causes an increase of the B-type of creatine kinase. It can be concluded that cyclic GMP, generated via the nerve, has an important role in maintaining muscle weight.