Dorsal root ganglion (DRG) neurons express receptors for bradykinin and capsaicin, both algesic substances. Administration of bradykinin or capsaicin to neurons cultured from embryonic rat DRG stimulated the production of cyclic GMP but did not affect the production of cyclic GMP in nonneuronal DRG cultures. Bradykinin-evoked cyclic GMP production was mediated by B2 receptors and was unaltered by indomethacin. Both bradykinin- and capsaicin-stimulated cyclic GMP production required Ca2+ and was inhibited by methylene blue. Furthermore, methylene blue attenuated basal cyclic GMP production in DRG neurons, suggesting tonic cyclic GMP production in these cells. L-NG-monomethyl arginine inhibited both bradykinin- and capsaicin-stimulated cyclic GMP production as well as basal cyclic GMP production. These findings suggest the involvement of a nitrosyl compound in bradykinin- and capsaicin-stimulated cyclic GMP production and in tonic cyclic GMP production in DRG neurons.