The irritant action of capsaicin is mediated by the vanilloid receptor, VR1, which is expressed in sensory neurons termed nociceptors. Capsaicin also desensitizes nociceptors and, thus, is useful clinically as an analgesic. Given the potential importance of VR1 in pain, we have cloned the human capsaicin receptor, hVR1, from a human dorsal root ganglia (DRG) cDNA library. Human VR1 protein is 85% identical to the rat VR1 and many of the amino acid differences are concentrated at the amino and carboxyl termini, VR1 is expressed in DRG as an approximately 4.2 kilobase RNA, and is also expressed in the central nervous system and in the kidney. Capsaicin (EC50 = 853 nM), low pH (<5.5), and noxious heat (44C) activate hVR1 expressed in Xenopus oocytes. Subthreshold pH (6.4) sensitizes VR1 to capsaicin (EC50 = 221 nM). This study demonstrates the similarity of human and rat VR1 in integrating multiple noxious stimuli.