1. The effects of capsaicin on voltage-gated Ca2+ currents (ICa), and intracellular Ca2+ concentrations [( Ca2+]i) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp-microfluorometric recordings. 2. Under voltage-clamp conditions, capsaicin (0.1-10 microM) caused a concentration-dependent decrease in the magnitude of the ICa, an elevation in the holding current (Ih) and a concomitant rise in the [Ca2+]i in most cells examined. Repeated application of capsaicin produced marked desensitization. 3. Some decrease in the ICa produced by capsaicin was also observed when the rise in [Ca2+]i was buffered with EGTA or BAPTA and when Ba2+ was used as the charge carrier; under these conditions the desensitization previously observed was smaller. 4. The decrement in voltage-gated current was smaller in Ba2+ containing solutions than in Ca2+ containing solutions suggesting that the capsaicin-induced influx of Ca2+ partially mediated the observed decrease in the voltage-gated current. In cells which showed a marked response to capsaicin an outward (positive) current was sometimes observed upon depolarization from -80 to 0 mV. This effect was consistent with an outward movement of cations through the capsaicin conductance pathway which may also account, in part, for the apparent reduction in ICa by capsaicin. 5. The effects of capsaicin under voltage-clamp conditions were prevented by ruthenium red (1 microM). 6. Under current clamp conditions, capsaicin depolarized and caused a rise in [Ca2+]i in the majority of DRG cells examined. Both of these effects could be prevented by ruthenium red (500 nM). 7. It is concluded that capsaicin reduces the Ic. of rat DRG neurones primarily by indirect mechanisms.