We have previously found that volume-regulated chloride current (VRCC) is involved in cell cycle progression and cell proliferation. This study was to examine the effect of Tween 80, a nonionic surfactant, on VRCC and cell proliferation in rat basilar artery smooth muscle cells (BASMCs). VRCC was recorded using a whole-cell patch clamp. Cell proliferation and cell cycle were determined by CCK-8, cell count and flow cytometry. The results showed that endothelin-1 promotes cell cycle transition from the G0/G1 phase to the S phase and significantly increases VRCC in BASMCs. The effect of Tween 80 on VRCC is reversible and concentration dependent. However, this chemical has no effect on the calcium-activated chloride channel. Tween 80 also concentration-dependently inhibits BASMCs proliferation and arrests cells in the G1/S checkpoint. The antiproliferative effect is paralleled with the inhibitory effect on VRCC. Our study demonstrates that the inhibitory effect of Tween 80 on VRCC contributes importantly to arrest of the cell cycle and prevention of cell proliferation. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.