Glial cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor shown to rescue developing and adult motoneurons in vitro and in vivo from programmed and injury-induced cell death. To test whether GDNF would rescue adult mammalian sensory and motor neurons from physiological consequences of injury, the tibial nerve of rats was axotomized and, after a 10 day delay to permit injury processes to proceed, vehicle or GDNF was supplied directly to the nerve for 2 or 4 weeks or GDNF intrathecally for 2 weeks. Conduction velocity (CV) of both sensory and motor axons declined during the initial 10 days, and even more so if then treated with vehicle. Treatment with GDNF resulted in marginal improvement of sensory axon CV. CV of motor axons recovered significantly in a dose- and time-dependent manner. The results suggest that GDNF may have therapeutic potential in the treatment of peripheral neuropathies.