Hypotonic exposure provokes mobilization of arachidonic acid, production of reactive oxygen species (ROS), and a transient increase in taurine release in Ehrlich Lettre cells. The taurine release is potentiated by H₂O₂ and the tyrosine phosphatase inhibitor vanadate and reduced by the phospholipase A₂ (PLA₂) inhibitors bromoenol lactone (BEL) and manoalide, the 5-lipoxygenase (5-LO) inhibitor ETH 615139, the NADPH oxidase inhibitor diphenyl iodonium (DPI), and antioxidants. Thus, the swelling-induced taurine efflux in Ehrlich Lettre cells involves iPLA₂/sPLA₂ plus 5-LO activity and modulation by ROS. Vanadate and H₂O₂ stimulate arachidonic acid mobilization and vanadate potentiates the ROS production in Ehrlich Lettre cells and NIH3T3 fibroblasts under hypotonic conditions. However, vanadate-induced potentiation of the volume-sensitive taurine efflux is in both cell types impaired in the presence of BEL and DPI and following restoration of the cell volume. Thus, potentiation of the volume-sensitive taurine efflux pathway following inhibition of tyrosine phosphatase activity reflects an increased arachidonic acid mobilization and ROS production for down-stream signaling. Vanadate delays the inactivation of the volume sensitive taurine efflux in NIH3T3 cells and this delay is impaired in the presence of DPI. Vanadate has no effect on the inactivation the swelling-induced taurine efflux in Ehrlich Lettre cells. It is suggested that an increased tyrosine phosphorylation of a regulatory components of the NADPH oxidase leads to an increased ROS production and a subsequent delay in the inactivation of the volume-sensitive taurine efflux pathway and that the NADPH oxidase or anti-oxidative capacity differ between NIH3T3 and Ehrlich Lettre cells.