In a number of sensory neuron preparations, Ruthenium red (RR) selectively attenuated the response to capsaicin. First, RR (100 nM) reversibly abolished capsaicin but not bradykinin induced increases in [Ca2+]i measured in single DRG neurons from neonatal rats, using the calcium sensitive dye Fura-2. Second, RR completely but reversibly abolished capsaicin-activated single ion channel currents measured in membrane patches from rat DRG neurons. This effect of RR differed from that produced by lanthanum. Finally, in a neonatal rat spinal cord-tail preparation maintained in vitro, RR selectively attenuated the activation of peripheral nociceptors produced by capsaicin but not by bradykinin or noxious heat. These data indicate that RR inhibits capsaicin mediated effects on sensory neurons by an action on the plasma membrane to prevent opening of capsaicin activated ion channels.