Whole cell patch-clamp recordings of calcium-activated chloride current [I_Cl(Ca)] were made from adult sensory neurons of naive and axotomized mouse L₄–L₆ lumbar dorsal root ganglia after 1 day of culture in vitro. A basal I_Cl(Ca) was specifically expressed in a subset of naive medium-diameter neurons (30–40 μm). Prior nerve injury, induced by sciatic nerve transection 5 days before experiments, increased both I_Cl(Ca) amplitude and its expression in medium-diameter neurons. Moreover, nerve injury also induced I_Cl(Ca) expression in a new subpopulation of neurons, the large-diameter neurons (40–50 μm). Small-diameter neurons (inferior to 30 μm) never expressed I_Cl(Ca). Regulated I_Cl(Ca) expression was strongly correlated with injury-induced regenerative growth of sensory neurons in vitro and nerve regeneration in vivo. Cell culture on a substrate not permissive for growth, d,l-polyornithine, prevented both elongation growth and I_Cl(Ca) expression in axotomized neurons. Regenerative growth and the induction of I_Cl(Ca) expression take place 2 days after injury, peak after 5 days of conditioning in vivo, slowly declining thereafter to control values. The selective expression of I_Cl(Ca) within medium- and large-diameter neurons conditioned for rapid, efficient growth suggests that these channels play a specific role in postinjury behavior of sensory neuron subpopulations such as neuropathic pain and/or axonal regeneration.