The endocytotic activity of skeletal muscle fibres and its relation to the denervated endplate region has been studied using horseradish peroxidase (HRP) as marker for endocytosis. In muscles denervated for a short time period (10-20 days) HRP-uptake occurred in small segments of the muscle fibres near the centre of the muscle (endplate region). After long-term denervation (6-12 months) similar segments with high endocytotic activity were seen preferentially in more peripheral parts of the muscle fibres. Ultrastructural characteristics of segments with high endocytotic activity from long-term denervated muscle fibres include a proliferating transverse tubular system, HRP-containing bodies of different sizes with some very large vacuoles extending over several sarcomeres. These characteristics are similar to those described previously for HRP-uptake in the endplate region of short-term denervated muscle (Tågerud et al., J. Neurol. Sci., 75 (1986) 141) except that no recognizable endplate structures were observed in the present study. The results are discussed in relation to the fate of the denervated endplate and the receptive capacity for synapse formation in long-term denervated muscle.