Adult rat skeletal muscle does not express detectable levels of neural cell adhesion molecule (N-CAM) and membrane activity mediated by nerve appears to repress the N-CAM gene. N-CAM expression in skeletal muscle can however be reinduced by hypothyroidism. Thyroidectomised rats re-express N-CAM mRNAs of 5.2 and 2.9 kb and Western blot analysis showed protein bands of 125 and 155 kDa. Immunofluorescence analysis also showed high levels of N-CAM in the sarcolemma. These changes in N-CAM expression could be reversed by treatment of hypothyroid rats with thyroxine. Thus thyroid hormones as well as neural influences appear to control N-CAM expression in skeletal muscle.