The effect of peripheral axotomy on the expression of the class III β-tubulin gene in adult dorsal root ganglion (DRG) neurons was examined. Of the 5 isotypic classes of β-tubulin expressed in the mammalian nervous system, only the class III β-tubulin is neuron specific. While information about the expression of several of the tubulin genes during neuronal development and regeneration has become available recently, very little is known about the expression of βIII-tubulin during axonal regeneration. To explore this issue, we examined axotomy-induced changes in βIII-tubulin mRNA levels in adult rat lumbar dorsal root ganglion (DRG) neurons at different times (1–28 days) after unilateral sciatic nerve crush using northern blotting of total RNA and quantitative in situ hybridization. These studies showed an initial decrease in βIII-tubulin mRNA levels in axotomized DRG neurons as compared to contralateral controls at 1 day after injury followed by robust increases in βIII-tubulin mRNA levels relative to contralateral controls from 1 to 4 weeks after injury. We postulate that βIII-tubulin may play an essential role in axonal growth because of its unique neuron-specific pattern of expression and its substantial increase in neurons that have been stimulated to regrow their axons. © 1993 Wiley-Liss, Inc.