A dose-dependent loss of vanilloid receptors (specific [3H]resiniferatoxin binding sites) was found in sensory ganglia of rats 24 h after s.c. administration of resiniferatoxin (RTX), an ultrapotent capsaicin analog. This receptor loss displayed an ED50 of 30 micrograms/kg both in dorsal root and trigeminal ganglia; the ED50 was 6-fold higher than the ED50 for loss of the neurogenic inflammatory response and 30-60-fold higher than the ED50 for desensitization in the standard eye-wiping (chemogenic pain) response. The receptor loss appeared later (24 h) than the loss of the physiological responses (6 h) and showed modest recovery (to 20-30% of control levels) over the following 4 weeks. This vanilloid receptor loss may represent a novel, specific mechanism for vanilloid-induced chronic desensitization.