Intraneural injection of pure glycerol induces Wallerian degeneration with subsequent regeneration. In agreement with other reports, we observed an increase in endoneurial polyunsaturated fatty acids 8 days after the glycerol injection. Levels then fell until day 30. After a period of 5 months, there was an increase in C18:2(n-6) in the intrafascicular tissue, concomitant with a marked fall in this fatty acid in the remaining extrafascicular perineurium. The rise in C18:2(n-6) in endoneurium correlated with infiltration of this tissue by perineurial cells. Interactions between perineurium and endoneurium during nerve regeneration are discussed.