A variety of tannin and lignin-related compounds were compared for their ability to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of apoptosis), using agarose gel electrophoresis and a fluorescence activated cell sorter. Monomeric, dimeric, trimeric and tetrameric hydrolysable tannins induced nucleosome-sized DNA fragmentation in HL-60 cells, more potently than condensed tannins. The highest activity was detected in gallic acid, a component unit of tannins. Natural lignified materials, except for caffeic acid and its dehydrogenation polymer, showed much weaker activity. Protein-bound polysaccharide (PSK) was inactive. Gallic acid induced DNA fragmentation in four human myelogenous leukaemic cell lines, but not in human T-cell leukaemia and erythroleukaemia cell lines. Ca2+ depletion from the culture medium slightly, but significantly, reduced the apoptosis-inducing activity of gallic acid, but did not significantly affect that of tannic acid or caffeic acid. After treatment with gallic acid, intracellular Ca2+ concentration was significantly elevated. The apoptosis-inducing activity of polyphenols may further emphasize their medicinal efficacy.