Voltage-activated calcium currents were recorded in cultured rat dorsal root ganglion neurones using the whole cell clamp technique. The effect of inclusion in the patch pipette of the non-hydrolysable guanine nucleotide analogues, guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S) and guanosine 5'-O-2-thiodiphosphate (GDP-beta-S) was examined both on ICa itself and on the ability of the GABAB agonist baclofen to inhibit ICa. In the absence of either guanine nucleotide, the maximum ICa recorded at between -20 and 0 mV consists of two components, a rapid transient and a non- or slowly inactivating current. Baclofen (50 microM) inhibited peak ICa by 37.5 +/- 4.7%. In the presence of 500 microM GTP-gamma-S the inactivating calcium current was largely absent and the effect of 50 microM baclofen was increased to a 78.1 +/- 2.3% inhibition. GDP-beta-S had opposite effects to GTP-gamma-S. The results suggest that the calcium channels in these neurones are associated with a GTP binding protein which regulates the calcium currents and mediates the inhibitory effect of neurotransmitters.