Natural phenolic compounds, curcumin and gallic acid, were compared for their cytotoxic activity in relation to their radical modulating activity. These two compounds induced apoptotic cell death in human promyelocytic leukemic HL-60 cells and human oral squamous carcinoma HSC-4 cells. Curcumin was more cytotoxic than gallic acid. Catalase reduced significantly the cytotoxic activity of gallic acid, but not that of curcumin. ESR spectroscopy demonstrated that curcumin produced radicals under alkaline conditions, scavenged the superoxide anion radical, and enhanced the radical intensity of sodium ascorbate at higher concentrations. As compared with curcumin, gallic acid produced higher amounts of radicals and more efficiently scavenged the superoxide anion radical. Gallic acid reduced the radical intensity of sodium ascorbate, suggesting a possible interaction between these two compounds. These data suggest that curcumin and gallic acid induce apoptosis by different mechanisms.