The spatial distribution of horseradish peroxidase (HRP) uptake has been studied by light- and electron microscopy in the denervated hemidiaphragm of the mouse. Segments with high HRP uptake were observed in a band centrally located in the denervated muscle. This distribution is similar to the well-known innervation pattern of the diaphragm. Ultrastructural studies demonstrated a high incidence of postsynaptic folds in close proximity of fibre areas with high intracellular content of HRP. 8–12 days after denervation a large number of fibres showed segments of high HRP uptake. 2–4 days after denervation very few such segments were observed. Biochemical studies also demonstrated an increase in HRP uptake after denervation occurring primarily in the endplate region. The activities of the lysosomal enzymes N-acetyl-β-d-glucosaminidase, acid phosphatase and cathepsin D all increased after denervation, most prominently in the endplate region.It is suggested that the observed segmental uptake of HRP and lysosomal activation reflects a process for rapid membrane turnover in denervated muscle.