The effect of copper sulfate (CuSO4) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55) was investigated. HVE cells were collected from umbilical veins by enzymatic digestion with collagenase. The viability, subsequent growth and DNA synthesis of both cell types were inhibited concentration-dependently by the addition of copper. The cytotoxic effect of copper on the morphology of these cells was also concentration-dependent. However, the cytotoxic effect of copper on the viability, subsequent growth and DNA synthesis was greater in HVE cells than in HAIN-55 cells. These results suggest that HVE cells are more susceptible to concentration-dependent copper cytotoxicity than HAIN-55 cells are, and that copper could induce vascular endothelial injury, which may be involved in the pathogenesis of cardiovascular disease.