The effect of nitric oxide (NO) on calcium current (I-Ca) and intracellular calcium concentration ([Ca2+](i)) in primarily cultured dorsal root ganglion (DRG) neurons was investigated from neonatal rats. I-Ca and [Ca2+](i) were simultaneously recorded using perforated-patch technique in combination with fluorescence measurement from single DRG neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), inhibited I-Ca in small-diameter neurons without significant change in voltage-dependence of activation and activation time constants. SNP and SNAP also reduced the transient [Ca2+](i) peak accompanied by I-Ca. Inhibition by NO was reproducible, but gradually desensitized. In some DRG neurons, SNP and SNAP increased basal [Ca2+](i) in concentration of 10 mu M with little effect on NO-induced inhibition of I-Ca. 8-Br-cGMP, a permeable cGMP analog, mimicked the effects of SNP and SNAP. These results suggest that, in DRG neurons, NO has inhibitory effect on Ic., which is independent of NO-induced increase of basal [Ca2+](i), through cGMP-dependent pathway.