The volume-regulated Cl(-) current (I(Cl.vol)) is responsible for the transmembrane Cl(-) transport that is involved in cell volume regulatory mechanisms. Although the regulation of cell volume is a fundamental function of healthy cells for maintaining constant size, the molecular genetic identification of I(Cl.vol) is still being debated. Recent studies in vascular smooth muscle support the idea that ClC-3, a member of the voltage-gated ClC Cl(-) channel family, is the molecular component involved in the activation or regulation of I(Cl.vol). Moreover, gene-targeting studies in vascular smooth muscle cells (VSMCs) and other cell types indicate emerging roles of ClC-3 in cell proliferation and apoptosis. These findings indicate that ClC-3 might be involved in modulating vascular remodeling in hypertension and arteriosclerosis.