Vertebrate rod and cone photoreceptors hyperpolarize when illuminated. However, synaptic input from horizontal cells can depolarize cones and even elicit action potentials. Using the whole-cell tight-seal recording technique, we determined that, in solitary cones isolated from a lizard retina, action potentials can be generated by depolarizing current steps under conditions where only two ionic currents are activated. A dihydropyridine-sensitive, inward Ca2+ current that activates at potentials positive to -40 mV can regeneratively depolarize the cell. Subsequently, a SITS-sensitive, Ca2(+)-dependent outward Cl- current repolarizes the cell. We suggest that these ionic currents may help explain lateral inhibition in the retina.