1. The pharmacological properties of excitatory amino acid responses on ganglion cells dissociated from the rat retina were examined with the use of the whole-cell voltage-clamp technique. 2. L-Glutamate at a concentration of 50 microM produced inward non-desensitizing currents at negative holding potentials in nearly every cell tested (83%, n = 18) In physiological solutions, L-glutamate responses reversed at approximately -9 mV, and higher concentrations of this agonist introduced a desensitizing component to the response. 3. At negative holding potentials, kainate (25-125 microM) produced inward currents in all of the cells tested (n = 37). These currents never desensitized, even at high agonist concentrations, and reversed near -6 mV. Currents induced by 50 microM-kainate were reversibly antagonized by kynurenate (100-300 microM) but not by 100 microM-2-amino-5-phosphonovalerate (APV). 4. Quisqualate generated smaller, non-desensitizing currents in only 50% of the cells tested (n = 38). Quisqualate responses reversed in polarity near -4 mV and were maximal at an agonist dose of 25 microM, with higher concentrations introducing a rapidly desensitizing component without a detectable increase in amplitude. Currents produced by quisqualate at a concentration of 50 microM were not antagonized by either 750 microM-kynurenate or 100 microM-APV. 5. N-Methyl-D-aspartate (NMDA) produced inward currents at negative holding potentials in 68% of the cells tested (n = 31), but only when magnesium was excluded from the extracellular medium. NMDA currents were non-desensitizing at agonist concentrations of up to 200 microM, with higher concentrations introducing a rapidly desensitizing component. NMDA (200 microM) responses were blocked by APV (100 microM) and kynurenate (300 microM) and reversed near -1 mV. 6. Responses generated by kainate (50-125 microM) were antagonized by quisqualate (30-250 microM). This antagonism occurred even in cells having no measurable response to quisqualate alone, suggesting the possibility that quisqualate may be acting both as an agonist, in the 50% of the cells that have the quisqualate-specific receptor, and as an antagonist, at the kainate-specific site on all cells.(ABSTRACT TRUNCATED AT 400 WORDS)