We clarified the roles of insulin-like growth factor (IGF) I and II in peripheral neural regeneration after axotomy using cultured adult DRG explants either with or without associated nerve bundles. When IGF-I was applied at concentrations of 1-10 nM to DRG explants without associated nerve bundles in a serum-free medium, clear enhancement of neural regeneration from both central and peripheral transected nerve terminals was seen. When the same concentrations of IGF-I were applied to DRG explants with associated nerve bundles this enhancement was reduced at central sites and increased at peripheral sites. Neural survival was not affected by IGF-I in any of these culture systems. In comparison with IGF-I, there was no specific effect of IGF-II on neurite regeneration.