We have examined expression of Tα1 α-tubulin mRNA in the rat superior cervical ganglion (SCG) to determine whether changes in gene expression accompany neuronal sprouting and to investigate factors that regulate growth-associated genes in intact neurons. Northern blot analysis demonstrates that levels of Tα1 α-tubulin mRNA increase in the uninjured SCG following transection of contralateral neurons that project to bilaterally innervated, but not unilaterally innervated target organs. The observed increase in uninjured neurons is associated with collateral sprouting, as measured by increased tyrosine hydroxylase immunoreactivity within the pineal gland. These data suggest that targetderived factors may regulate Tα1 mRNA in sprouting neurons. Consistent with this hypothesis, systemic NGF treatment of neonatal animals over a developmental interval when Tα1 α-tubulin mRNA normally decreases led to a 5- to 10-fold increase in Tα1 mRNA levels in developing sympathetic neurons. In addition, deafferentation of the SCG, which promotes neuronal sprouting in the ganglion, increases Tα1 mRNA in ganglia on the ipsilateral and contralateral sides. Together, these data demonstrate that Tα1 α-tubulin mRNA elevates as a function of neuronal sprouting, and that Tα1 mRNA expression in intact neurons can be regulated by extrinsic cues, including NGF and changes in connectivity. © 1990.