The effects of synaptic blocking agents on the antagonistic surround of the receptive field of cone photoreceptors were studied by intracellular recording in the retina of the turtle (Pseudemys scripta elegans). Illumination of a cone's receptive-field surround typically evoked a hybrid depolarizing response composed of two components: (1) the graded synaptic feedback depolarization and (2) the prolonged depolarization, a distinctive, intrinsic response of the cone. The locus of action of synaptic blocking agents was analyzed by comparing their effects on the light-evoked response of horizontal cells, the hybrid cone depolarization evoked by surround illumination, and the pure prolonged depolarization evoked by intracellular current injection. The excitatory amino-acid antagonists, d-O-phosphoserine (DOS) and kynurenic acid (KynA), suppressed the light responses of horizontal cells and eliminated the surround-evoked, hybrid cone depolarization without affecting the prolonged depolarization evoked by current injection. Cobalt at 5-10 mM suppressed horizontal cell responses and thereby eliminated surround-evoked cone depolarizations. Cobalt (5-10 mM) also blocked the current-evoked prolonged depolarization, suggesting that the intrinsic cone mechanisms responsible for the prolonged depolarization are likely to be calcium-dependent. Various GABA agonists and antagonists were found to have no effect on the surround-evoked depolarizations of cones. In contrast, a very low concentration of cobalt (0.5 mM) selectively suppressed the light-evoked feedback depolarization of cones without affecting horizontal cell responses or the current-evoked prolonged depolarization. Cobalt at 0.5 mM thus blocks the light-evoked action of the cone feedback synapse while sparing feedforward synaptic transmission from cones to horizontal cells. The implications of the present work for the possible neurotransmitters used at these synapses is discussed.