Two cytotoxic peptides, yaku'amides A (1) and B (2), were isolated from the marine sponge Ceratopsion sp. Their planar structures were elucidated on the basis of spectroscopic data, whereas the absolute configurations were determined by a combination of the Marfey's analysis and dansylation analysis of the total and partial acid hydrolysis products. The growth inhibitory profile of yaku'amide A against a panel of 39 human cancer cell lines was clearly unique and distinguished from other anticancer drugs.