The fine structure changes which occurred during denervation and reinnervation of neuromuscular junctions for a period of thirty weeks after nerve section were studied in muscles of the mouse foot.

Axons were absent by the end of the first week after nerve section and there was retraction of Schwann cells and perineural epithelial cells. The primary synaptic cleft became shallow, the secondary clefts, shorter and wider, but the basement lamina filling the subneural apparatus was unaltered. The characteristic thickening of the muscle surface membrane in the primary synaptic cleft persisted, and there were increased numbers of clustered ribosomes. A loss of coated vesicles was observed in the sole-plate sarcoplasm.

The earliest returning axon sprouts were first observed at three weeks and became numerous by four weeks. These originally contained few and variably sized synaptic vesicles but no coated vesicles. In the succeeding weeks the primary clefts deepened, the secondary clefts became elongated and narrower, and, by fifteen to thirty weeks, all neuromuscular junctions studied had normal fine structure.

No fine-structure evidence of de novo formation of neuromuscular junctions was obtained by electron microscopy, although occasional small neuromuscular junctions formed by escaped fibers were observed in dual-stained sections studied in the light microscope.

Persistence of tenuous processes of both Schwann and perineural epithelial cells in the immediate vicinity of denervated neuromuscular junctions appeared to play a major role in guiding returning axons to old sites of innervation.