In the fish retina, horizontal cell electrical coupling and light responsiveness is regulated by activation of dopamine D1 receptors that are located on the horizontal cells themselves. The effects of dopamine and dopamine D2 receptor agonists and antagonists on cone horizontal cell light responses were studied in vitro superfused goldfish retinas. Horizontal cell light responses and electrical coupling were assessed by monitoring responses to full-field stimuli and to small, centered (0.4 mm diam) spots of light, respectively. Dopamine (0.2-10 μM) application uncoupled horizontal cells and decreased their responses to full-field stimuli. Application of the D2 antagonist eticlopride (10-50 μM) produced similar effects, whereas quinpirole (0.1-10 μM), a D2 agonist, had the opposite effects. The uncoupling effect of eticlopride was blocked by prior application of SCH23390 (10 μM), a D1 receptor antagonist, and was eliminated after destruction of dopaminergic neurons by prior treatment of the retinas with 6- hydroxydopamine. The effects of these D2 drugs were observed following flickering light stimulation, but were not observed following sustained light stimulation. Application of the D2 antagonists sulpiride (0.5-20 μM) and spiperone (0.25-10 μM) uncoupled horizontal cells when the total concentration of divalent cations (Mg2+ and Ca2+) in the Ringer solution was 1.1 mM. However, when the concentration of divalent cartons was 0.2 mM, spiperone had no effect on the horizontal cells and sulpiride increased coupling. In contrast, eticlopride uncoupled the cells and decreased their light responsiveness irrespective of the concentration of divalent cartons. The effects of quinpirole also depended on the concentration of divalent cations; its coupling effect was reduced when the divalent cation concentration was increased from 0.2 to 1.0 mM. The results suggest that activation of D2 receptors in the fish retina by endogenous dopamine decreases dopamine release and is greater after flickering compared with sustained light stimulation. These D2 receptors thus function as presynaptic antoreceptors that inhibit dopamine release from dopaminergic cells. In addition, the results also indicate that the effectiveness of some D2 drugs at these receptors is dependent on the concentration of divalent cations.