AbstractA study, mainly by electron microscopy, has been made on the forelimb musculature of Ambystoma opacum larvae following removal of the presumptive limb innervation in the embryo. In the aneurogenic limbs, early development and differentiation of striated muscle occurs at the same rate as in normal animals. At the time of nerve ingrowth into the normal limb, both myotubes and differentiated myofibers of small diameter are present. With the failure to make contact with nerves, the aneurogenic muscle does not advance beyond the early myofiber stage and soon (1–2 weeks) begins to show signs of atrophy. As has been described in studies of denervated adult muscle, the breakdown seems to be in two phases overlapping in time. In the first, a degenerative autolysis takes place, leading to loss of striation. There is dissolution of the Z bands, followed by disorder of the myofilaments. During this process there is evidence of fragmentation of the muscle fiber, both into nucleated and anucleate portions; waste sarcoplasm is thought to be discarded into the intercellular spaces. Interestingly enough, with the techniques used, no sign of lysosomes was noted and only a few macrophages were seen. The second phase of muscle breakdown is one with characteristics of atrophy, where single myofibers undergo gradual reduction in diameter. This process seems to take place by detachment of filaments from the periphery of the fibers and by their subsequent breakdown in the interfibrillary spaces. Late stages of muscle deterioration show large areas of cytoplasm containing scattered ribosomes, small vesicles, and a few mitochondria. The final picture is of densely stained irregular nuclei surrounded by a thin rim of cytoplasm; the intercellular spaces contain a considerable amount of fibrous material. The cartilage and skin of the aneurogenic limb appear normal even after the latest stages of muscle deterioration.