The purpose of the present study is to observe the role of volume-sensitive Cl(-) channels in carboplatin-induced apoptosis in the human lung adenocarcinoma cell line A549 cells. Using patch clamp and apoptosis assays, we found that A549 cells underwent the process of apoptotic volume decrease (AVD) and apoptosis when treated with carboplatin or staurosporine (STS). This AVD and apoptosis process were blocked by chloride channel blockers, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3-phenyl propylamino)-benzoate (NPP B). Both carboplatin and STS treatment activated a Cl(-) current, which shows similar properties to hypotonicity-induced volume-sensitive Cl(-) current in A549 cells. In addition, carboplatin pretreatment augmented the magnitude of the hypoosmotic-induced volume-sensitive Cl(-) current. These results suggest that volume-sensitive Cl(-) channels may be responsible for the carboplatin-induced apoptosis in A549 cells by inducing the AVD process.