The expression of many myelin-specific molecules in Schwann cells is profoundly decreased following denervation. This study examines the early reexpression of myelin protein genes associated with reinnervation. Following sciatic nerve crush, the distal, regenerated nerve was divided into appropriate (2.5 or 5 mm) consecutive lengths in which gene expression was monitored using Northern blotting, in situ hybridization, and immunostaining. The spatial separation of the distal axon tip and the more proximally located Schwann cells showing initial upregulation of P0 mRNA was constant over the period of 5-13 days after crush at approximately 3-4 mm in fixed, processed material. Axons associated with Schwann cells showing the initial upregulation were completely or partially enveloped in Schwann cell cytoplasm, with very few having any degree of ensheathment. It is probable that only a limited axon-Schwann cell contact is required for induction of the myelin protein genes. Myelin-associated glycoprotein mRNA was upregulated prior to those for P0 and myelin basic protein which had similar time courses. Reexpression of galactocerebroside also preceded that for P0 mRNA. Signal abundance for all myelin proteins decreased in a proximal to distal direction from the crush site, and with time the "wave" of upregulation moved distally down the nerve. In the more proximal, remyelinating zones, the signal intensity exceeded that of the contralateral normal nerve. Signal intensity also varied considerably between adjacent, expressing Schwann cells. The data provide further evidence of the strong temporospatial relationship between axons and the regulation of myelin protein genes in Schwann cells.