Release of taurine in response to cell swelling induced by hyposmolarity was observed in cultured astrocytes. Efflux of 3H-taurine increased by 30% and 70% upon reductions in osmolarity of only 5% and 10%. Reductions in osmolarity of 20%, 30%, and 50% stimulated basal taurine release by 300%, 500%, and 1,500%, respectively. The properties of this volume-sensitive release of taurine were examined to investigate: 1) its association with K+ and Cl- fluxes, currently activated during volume regulation: 2) its relationship with Ca2(+)-dependent reactions; and 3) the mechanism of the taurine efflux process. Taurine release was unaffected by removal of Na+, Ca2+, or Cl-, by pimozide and trifluoperazine, or by agents disrupting the cytoskeleton. The K+ channel inhibitors barium, quinidine, tetraethylammonium, and gadolinium had no effect. Taurine release was reduced by furosemide, a blocker of K+/Cl- cotransport, but not by the more specific inhibitor, bumetanide. It was markedly reduced by the inhibitors of Cl- channels DIDS, SITS, and anthracene-9-carboxylate. Taurine efflux was pH-dependent, being reduced at low pH values. It was decreased at 4 degrees C but not at 14 degrees C or 20 degrees C. These results suggest that the volume-sensitive release of taurine is independent of K+ fluxes but may be associated with Cl- conductances. It also seems unrelated to Ca2(+)-dependent transduction mechanisms. The Na(+)-dependent taurine carrier apparently is not involved in the swelling-induced release process.