We report the cytotoxicity of the ginseng saponin metabolite, Compound K (20-0-D-glucopyranosyl-20(S)-protopanaxadiol, 1H901) on various human leukemia cell lines. Compound K had the most effect on U937, a human monocytic leukemia cell line among the tested cell lines. Compound K-treated U937 cells showed characteristics of apoptosis: an exposure of phosphatidylserine from the inner cell membrane to the outer cell membrane, the formation of apoptotic bodies and DNA fragmentation. Compound K induced apoptosis by up-regulating Box, disrupting the mitochondrial membrane potential, and by activating caspase 9 and caspase 3. Therefore, we suggest that Compound K inhibits U937 cell growth by inducing apoptosis through the up-regulation of Bax and caspase activation.