During the course of experiments related to muscle degeneration and regeneration we have become interested in the central core degeneration associated with tenotomy of skeletal muscle. This clear cut lesion, which closely resembles lesions found in human myopathies can be consistently reproduced in the rat soleus, is confined to slow fatigue resistant fibers and is associated with the speeding of muscle contraction. Available evidence indicates that a muscle is protected from this degeneration by denervation thereby suggesting that activity is important for its production. It has also been reported that recovery may occur even though length remains reduced. The association of the lesion with muscle shortening, a slow muscle, a particular fiber type, activity and recovery have suggested a series of experiments which will test each factor as a causative agent in its etiology. Preliminary results show that recovery in the tenotomized rat soleus is associated with a reduction in sarcomere numbers and a return to normal myofilament overlap. Using a similar approach the degree of adaptation to shortening of fast nonsusceptible muscles will be explored. The involvement of a single fiber type will be investigated by cross-reinnervation of susceptible and non-susceptible muscles by each others nerves and by modifying the fiber type by surgical and endocrinological methods. By subjecting tenotomized and denervated muscles to chronic in vivo stimulation the role of different stimulus patterns, which also determine fiber type will be evaluated. Because it has been shown that in single fibers stimulated below slack length only peripheral myofibrils contract we intend to check the integrity of the T-system in the stimulated but shortened soleus muscle. We hope that these experiments will define the causative factors in the experimental lesion and thus improve its value as a model of the clinical lesion. Unrelated experiments into the part played by degenerating nerve tissue in the production of degenerative changes in adjacent muscle are also planned. The results will be important in the interpretation of a number of experiments related to the trophic influence of nerve on muscle.