Bacterial phosphotriesterases are enzymes that hydrolyse phosphotriester-containing organophosphate pesticides, Resiniferatoxin is a vanilloid that desensitises nociceptive neurons, By screening a rat cDNA library with labelled resiniferatoxin, we unexpectedly isolated a novel rat phosphotriesterase homologue, here named rpr-1, that encodes a 349 amino acid, 39 kDa protein (confirmed by in vitro translation), Northern blotting and in situ hybridisation show expression primarily in proximal tubules of the kidney, in which rpr-1 distribution correlates with resiniferatoxin-binding activity. These results suggest an unsuspected link between the phosphotriesterase enzyme family and resiniferatoxin toxicity and pharmacology. (C) 1997 Federation of European Biochemical Societies.