Under a variety of pathological conditions, glial cells of the retina proliferate. Although glial cell proliferation may play a role in a number of important retinal disorders, the regulation of this proliferative response is understood poorly. We examined the possibility that the function of certain ion channels in retinal glial cells may be linked with the induction of proliferation. Experiments were performed on glial cells derived from the adult rat retina and maintained in culture. The cells stained positively by immunocytochemistry with antibodies specific for glial fibrillary acidic protein and for Muller cells. Patch clamp studies of these retinal glial cells demonstrated the presence of a large conductance, calcium-activated potassium channel that is sensitive to tetraethylammonium, a classical blocker of potassium channels. The activity of this type of potassium channel was monitored by patch clamp recordings in the cell-attached configuration before and after exposure of the glial cells to a mitogenic conditioned medium. Exposure to this conditioned medium was associated with a marked increase in the activity of the ion channel. A possible link between the activity of potassium channels and the action of mitogens was suggested further by the finding that tetraethylammonium significantly blocked the proliferative response of retinal glial cells to the conditioned medium. Our findings support the hypothesis that there is a link between the biophysical processes involved in ion channel activity and the proliferation of retinal glial cells.