Binding of [3H]resiniferatoxin was seen by autoradiography in sections of rat dorsal root ganglia and the superficial dorsal horn of the spinal cord. Membranes from rat dorsal root ganglia and spinal cord, but not other tissues, had saturable high-affinity binding sites for [3H]resiniferatoxin. A series of capsaicin analogues competed for these sites. The sites probably correspond to capsaicin receptors. Systemic pretreatment of rats with capsaicin caused loss of capsaicin sensitivity in sensory neurons and a reduction in binding of resiniferatoxin to rat dorsal root ganglia, measured by binding assays and autoradiography. Adult rat dorsal root ganglion neurons cultured without nerve growth factor also lost their capsaicin-sensitivity and showed reduced resiniferatoxin binding. Therefore, capsaicin responses in sensory neurons may be regulated by nerve growth factor through control of the number of capsaicin receptors.