A role for endogenous dopamine in the control of rod and cone contributions to a second-order retinal neuron, the horizontal cell (HC) was studied in the Xenopus retina. Relative rod and cone contributions were estimated from HC responses to scotopically balanced 491- and 650-nm flashes. In eyecups prepared in light then placed in darkness, cone input to the HC slowed and diminished on a time scale of hours. The decline in cone input was balanced by a slow growth of rod input to the HC. Administration of D-amphetamine, a dopamine releasing agent, restored the light-adapted waveform. The kinetics of slow light adaptation were examined by recording HC responses from eyecups that had been dark-adapted previously for 11-14 h. When test flashes fell on a dark field, cone input to the HC grew for 2-4 h, reached a plateau, and later declined. If, however, flashes were superimposed on a weak background field, cone input to the HC continued to increase monotonically at about 10%/h. This increase was abolished by superfusion with a nonspecific dopamine receptor blocker, cis-flupenthixol (50 microM), resulting in the complete suppression of cone-to-horizontal cell synaptic transfer and the enhancement of rod-to-horizontal cell communication. Subcutaneous injection of reserpine, a drug that depletes dopamine stores (2 mg/kg on 1-4 successive days), or intraocular injection of the dopamine neurotoxin, 6-hydroxydopamine (10-30 micrograms) slowed and reduced the amplitude of cone input to the HC, even in completely light-adapted eyes.(ABSTRACT TRUNCATED AT 250 WORDS)