Age-related differences in proliferative responses of Schwann cells during Wallerian degeneration were investigated in the mouse sciatic nerves after nerve-transection at 3, 10 and 60 days of age, corresponding to the periods of early myelination, active myelination and post-myelination. As assessed by thymidine incorporation for the first 24 h in culture, Schwann cells from adult nerve proliferated rapidly within day 1 post-transection and reached a peak at day 3. In the nerves from neonatal or suckling mice, however, division rate of Schwann cells declined after transection, and was even less in the transected nerves than in the contralateral uninjured nerves. The reduction in thymidine uptake by Schwann cells was more pronounced in nerves sectioned at postnatal day 3 than those sectioned at day 10. By contrast, fibroblasts divided rapidly following transection regardless of age. These data suggest that mitogens from myelin components are important for proliferation of Schwann cells and that in the degenerating nerves of young mice, mitotic capacity of Schwann cells declined due to not only a loss of axonal mitogens but also the paucity of mitogens from myelin components. Proliferation of fibroblasts is likely to be stimulated by more general growth-promoting polypeptides common to any other tissues during wound repair.