GABAA and GABAC receptors were studied on cultured or freshly isolated rat retinal bipolar cells. The cells displayed GABA-induced whole-cell currents, which were only partially blocked by high concentrations (100 microM) of the GABAA receptor antagonist bicuculline. The bicuculline-resistant (GABAC) component was insensitive to the GABAA receptor modulators flunitrazepam (1 microM) and pentobarbital (50 microM). The bicuculline-sensitive portion of the current was strongly augmented by both drugs, indicating that it was mediated by conventional GABAA receptors. The GABAC and GABAA receptor subtypes displayed a 7-fold difference in their binding affinity for GABA, the EC50 values being 4.2 microM and 27.1 microM, respectively. The Hill coefficient was approximately 2 for both receptors. The bicuculline-insensitive GABAC receptors were markedly blocked by 100 microM picrotoxinin, 2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide (SR-95531) and gamma-hexachlorocyclohexane, drugs known to be antagonists of GABAA receptors. Examination of single-channel currents indicated main-state conductances of 7.9 pS and 29.6 pS for GABAC and GABAA receptors, respectively. The pore diameter of open GABAC receptor channels was 5.1 A, i.e. close to the value of 5.6 A reported for the GABAA receptor. These results demonstrate that rod bipolar cells possess two populations of pharmacologically distinct GABA receptors, GABAA and novel-type GABAC receptors, which might subserve different physiological functions in controlling visual transduction in the retina.