To analyze the possible influence of nerve growth factor (NGF) on neurofilament synthesis in primary sensory neurons, adjacent cryostat sections of lumbar dorsal root ganglia (DRG) from adult rats were processed for either NGF-receptor radioautography or in situ hybridization with a neurofilament cDNA probe. Labeling by both procedures was quantified with computer assistance for approximately 300 neurons in each of selected ganglia. For uninjured neurons, no correction was detected between NGF binding and neurofilament mRNA, even after infusion of NGF into the lumbar subarachnoid space for 1 week. One or 3 weeks after sciatic nerve transection, neurofilament labeling densities in large DRG neurons were sharply reduced and the normal bimodal pattern in frequency histograms had become unimodal. Intrathecal infusion of NGF counteracted this injury-induced reduction of neurofilament mRNA but only in neurons with high-affinity NGF receptors. To explain the effects of NGF on axotomized neurons and the normal diversity of neurofilament gene expression among neurons with NGF receptors, we postulate that NGF permits NGF-sensitive DRG neurons to respond differentially to a second factor stimulating neurofilament synthesis.