A depsipeptide, polydiscamide A (1), composed of 13 amino acids including a novel amino acid 3-methylisoleucine, was isolated from a Caribbean sponge, Discodermia sp. Its structure was elucidated by means of spectroscopic, chemical degradation, and derivatization techniques. Polydiscamide A inhibits the in vitro proliferation of the cultured human lung cancer A549 cell line.