1. The effect of serotonin (5HT) was studied on high-threshold Ca2+ channel currents in a subpopulation of acutely isolated rat dorsal root ganglion cell bodies that had long-duration action potentials, lacked IH current, were capsaicin-sensitive, and thus resembled C-type nociceptors. 2. In these neurons, 10 microM 5HT inhibited peak high-threshold Ca2+ channel currents by 61.5 +/- 6.9% (mean +/- SE), (n = 7). The effects of 5HT were mimicked by 1 microM (+)8-hydroxy-2-(di-n-propylamino)-tetralin HBr [(+)8-OH-DPAT] in five neurons tested, and the effects of 1 microM (+)8-OH-DPAT were antagonized by 100 nM 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine HBr (NAN-190) in six neurons tested. 3. The above data leads us to hypothesize that 5HT, released into the spinal cord by descending systems, may produce antinociception by inhibiting Ca2+ entry into afferent terminals of nociceptors via activation of 5HT1A receptors.