We examined the effects of adenosine, a putative mediator of neuroprotection during cerebral ischemia, on the electrophysiological characteristics of retina-retinal pigment epithelium-choroid preparations obtained from 1-7 day-old chick and maintained in vitro. Our experiments produced the following results. First, superfusion of the retinal surface with adenosine (0.1 mM) increased the trans-tissue potential. The trans-epithelial (but not the trans-retinal) potential was also increased to the same magnitude with a time-course similar to that of the trans-tissue potential. Second, adenosine produced a depolarization of the epithelial basal plasma membrane with a concomitant decrease in its basal membrane resistance. Third, the trans-epithelial (but not the trans-retinal) c-wave in response to a light stimulus was augmented by adenosine. Adenosine reduced the hyperpolarization of the epithelial basal membrane, but had no effect on the extracellular concentration of K+ in the subretinal region. Fourth, the light-peak that was elicited with a 300 s light stimulus was also depressed by adenosine. Fifth, when 4,4'-diisothiocy anostilbene-2,2'-disulfonate (DIDS), a relatively selective inhibitor of Cl- channels, was perfused at 50 microM on the choroidal surface, adenosine-induced increases in the trans-tissue potential and the c-wave were both abolished. These results suggest that adenosine increased the Cl- conductance of the basal plasma membrane of the retinal pigment epithelium and thereby augmented the standing potential as well as the light-elicited membrane potentials of the retinal pigment epithelium, which seems to be involved in the pathophysiology of retinal ischemia.