Leptosins I and J, belonging to a series of epipolythiodioxopiperazines, have been isolated from the mycelium of a strain of Leptosphaeria sp. OUPS-4 attached to the marine alga Sargasssum tortile. Their relative stereostructures have been elucidated by chemical and spectral evidence. These compounds exhibited significant cytotoxic activity against cultured P388 cells.