In order to identify the transcription factors that may be involved in the development and differentiation of rat Schwann cells we examined the expression of c-Jun, Jun B, Jun D and the cAMP response element binding protein (CREB) in vivo and in vitro. We found that CREB was expressed at high levels throughout nerve development by both Schwann cells and their precursors. Jun family members, on the other hand, were expressed only at low levels in a few nuclei of the developing nerve. After sciatic nerve transection, however, c-Jun levels were rapidly up-regulated in many Schwann cells of the distal stump but CREB, Jun B and Jun D levels were not affected. When nerve contact was resumed after crush injury c-Jun levels returned to control values. Interestingly, unlike the situation in vivo, when Schwann cells were removed from the nerve and cultured, levels of all three Jun family members were rapidly up-regulated. This also occurred in Schwann cell precursors. In other experiments we found that Schwann cell c-Jun, but not Jun B or Jun D, expression was down-regulated by the adenylate cyclase activator, forskolin. In addition, we show that the forskolin induced down-regulation of c-Jun is not necessary for Schwann cell proliferation or myelination to occur.