Studies characterizing the types of GABA receptors present on cells isolated from the skate retina have allowed us to develop a working model of possible GABA interactions at the level of the outer plexiform layer (OPL). Earlier studies have shown an electrogenic GABA transport mechanism in horizontal cells presents a source of GABA in the OPL which could modulate feedback onto photoreceptors. GABA(A) receptors on Müller cells, or GABA(A) and/or GABA(C) receptors on bipolar cells. This model has been used for the interpretation of results of experiments in this study designed to test the role these interactions may exert on the electroretinogram (ERG). Simultaneous intracellular recording of the horizontal cell response (the S-potential) was used to monitor effects on photoreceptor transmitter release which would be altered if GABAergic photoreceptor feedback mechanisms were involved. Picorotoxin (50 microM), a chloride channel blocker which suppresses the responses of both GABA(A)Rs and GABA(C)Rs, reduced the ON (b-wave) component of the ERG substantially. Simultaneous intracellular horizontal cell recordings, however, showed no effect on their light-evoked response, suggesting that photoreceptor feedback is not involved in the picrotoxin effect on the ERG. On the other hand, even 100 microM bicuculline, a GABA(A)R antagonist produced no change in either the ERG or the horizontal cell response. This observation leads to the conclusion that the GABAARs on Miller cells and bipolar cells are not involved. Thus, there remains a distinct possibility that the ERG changes produced by picrotoxin are due to its ability to block the GABA(C)Rs on retinal bipolar cells.