Endothelin-1 (ET-1), an autocrine hormone synthesized by astrocytes, and endothelin-3 (ET-3), a highly homologous peptide produced by neurons, have both been shown previously to cause proliferation of these astrocytes in culture [Supattapone et al. (1989) Biochem. Biophys. Res. Commun., 165, 1115–1122; MacCumber et al. (1990) Proc. Natl. Acad. Sci. USA, 87, 2359–2363]. We now demonstrate, using 86Rb+ influx assays and single channel patch-clamp recording, that both endothelins–ET-3 and ET-1–can also open a charybdotoxin-sensitive, calcium-activated K+ channel of 15–40 pS in glial cells. The opening of this channel may be important for the regulation of [K+] in the brain microenvironment. Thus, the endothelins may be a general mediator of astroglial response to neuronal injury.