Lysosomes play an important role for the maintenance of a normal internal milieu in the cell. In neurons lysosomes are abundant in the perikaryon and dendrites, but have been observed to a much lesser degree in the axon. A general opinion has therefore formed among biologists interested in the nervous system that axonal material destined for degradation has to be transported to the neuronal perikaryon. The lysosomal occurrence and distribution at the level of the axon have, however, not been investigated systematically. This review summarizes recent morphological data based on light, fluorescence, and electron microscopic observations in peripheral nerve fibres of cats and rats providing evidence that node-paranode regions mainly along the peripheral parts of alpha motor axons, where the axon cross-section area decreases to 10-25% of internodal values, can control the passage and participate in a lysosome-mediated degradation of axonally transported materials directed towards the neuronal perikaryon. An important role is played by the paranodal axon-Schwann cell networks, which are lysosome-rich entities whereby the Schwann cells can sequester material from the axoplasm of large myelinated peripheral nerve fibres. The networks also seem to serve as depots for axonal waste products. The degradative ability of node-paranode regions in alpha-motor axons could be of some significance for the protection of the motor neuron perikarya from being flooded with and perhaps injured by indigestible materials as well as potentially deleterious, exogenous substances imbibed by the axon terminals in the muscle. A similar degradative capacity may not be needed in nerve fibres with synaptic terminals in the CNS where the local environment is regulated by the blood-brain barrier.