The mRNAs for 2 isotypes of alpha-tubulin, termed T alpha 1 and T26, are differentially regulated in the developing rat nervous system. T alpha 1 alpha-tubulin mRNA is expressed at high levels when neurons extend processes whereas T26 mRNA is expressed constitutively (Miller et al., 1987b). We have examined the expression of these 2 alpha-tubulin mRNAs in regenerating facial and sciatic motor neurons of the rat using Northern blot and in situ hybridization analyses. T alpha 1 alpha-tubulin mRNA is rapidly induced in axotomized motor neurons of the facial nerve: increased levels of mRNA are detectable 4 hr after a lesion is made 1.5 cm distal to the neuronal cell bodies. T alpha 1 mRNA levels are highest from 3-7 d postcrush and decline slowly to control levels following functional reinnervation of facial muscles. In contrast, T26 mRNA levels remain constant throughout the regeneration process. Total alpha-tubulin mRNA levels do not change until 1 d postaxotomy; otherwise the changes in expression are similar to T alpha 1 mRNA, although the relative increase is not as great. Enhanced T alpha 1 alpha-tubulin mRNA expression also occurs in motor neurons of crushed or tied sciatic nerve. Ligature or crush of the sciatic nerve leads to approximately the same peak in the expression of T alpha 1 mRNA at 7-15 d postaxotomy. Following the facial nerve transection, under conditions in which reinnervation is prevented, T alpha 1 alpha-tubulin mRNA levels remain elevated significantly longer than when the nerve is crushed. Taken together, the data indicate that T alpha 1 alpha-tubulin mRNA is rapidly induced following neuronal axotomy, remains elevated during the period of axonal regrowth, and is subsequently down-regulated at the approximate time of target contact. These results are reminiscent of changes in T alpha 1 mRNA that occur during neuronal development. This growth-associated pattern of T alpha 1 gene expression can be modified by inhibiting appropriate regeneration of the damaged nerve.