It has been proposed that horizontal cells of the vertebrate retina have a negative feedback synapse with cone photoreceptors. gamma-Aminobutyric acid (GABA) has been suggested to be a neurotransmitter of monophasic horizontal cells (a subtype of horizontal cells), which have direct connections with red-sensitive and green-sensitive cones. We have examined the feedback hypothesis by measuring the GABA sensitivity of photoreceptors. To eliminate interaction with other cells, we dissociated photoreceptors from the turtle retina enzymatically. The subtype of photoreceptors was identified unequivocally on the bases of the shape of the cell and the color of the oil droplets, which are known to correlate with the spectral sensitivity. Cells were voltage-clamped using "Giga-ohm sealed" suction pipettes in the whole-cell recording configuration, and membrane currents were measured in response to GABA applied ionophoretically at various positions on the cell. It was found that red-sensitive and green-sensitive cones were highly sensitive to GABA and that the sensitivity was localized at the axon terminals. GABA-sensitivity in blue-sensitive cones and in rods was very low. GABA-induced current reversed its polarity near the equilibrium potential of chloride, suggesting that GABA increased chloride conductance. Thus, our findings are consistent with the negative feedback hypothesis.