Peripherin is a 57 kDa type III intermediate-filament protein that is thought to play a role in axonogenesis both during development and following nerve injury (Oblinger et al., 1989; Escurat et al., 1990; Gorham et al., 1990; Troy et al., 1990b). We have used transgenic mouse technology to define peripherin gene sequences that are necessary for cell type-specific expression and for the increase in peripherin that occurs in response to axonal injury. Correct temporal and nervous system-specific expression resulted when 5.8 kilobases of peripherin 5' flanking sequence were linked to a reporter gene, but precise cell type-specific expression was achieved only when intragenic sequences were included. When intragenic sequences were present, peripherin transgenes were expressed in dorsal root ganglion neurons and spinal cord motor neurons and were upregulated in these cells following nerve injury.