Retinal bipolar cells are non-spiking interneurons that relay information from photoreceptors to amacrine and ganglion cells. In turn, bipolar cells receive extensive synaptic feedback from amacrine cells, some of which contain neuropeptides, including substance P. We have examined the effect of substance P on single bipolar neurons isolated from goldfish retina and find that substance P (0.1-1 nM) produced a voltage-dependent inhibition of calcium current in these cells. The inhibition was strongest at negative potentials, with the peak suppression occurring at -20 to -30 mV; at potentials positive to 0 mV, there was little effect on calcium current. Thus, the net effect was to shift the voltage range of activation of calcium current toward more positive potentials. The inhibition of calcium current by substance P required GTP in the patch pipette and was blocked by internal GDP-beta-S. Similar effects on calcium current were observed with somatostatin and metenkephalin, which are also found in amacrine cells.