The aqueous alcohol extract of the soft coralSinuZ&a fhxibitis from Hayman Island on the Great Barrier Reef of Australia has shown' confirmed antineoplastic activity in the National Cancer Institute's in vivo bioassay against P-388 lymphocytic leukemia (PS test). We have fractionated this extract using the guidance of bioassays in NCI's in vitro PS and RB (cytotoxicity) test systems, and have isolated three active principles, all cembranolides. (I) and dihydrosinularin (II), are new compounds. The third, sinulariolide reported previously by Tursch et al. 2 Two of them, sinularin (III), has been The isolation of this group of compounds entailed a series of solvent partitions and column chromatographies monitored at each step by in vitro bioassay. Bioactivity was first concentrated into the chloroform phase of a water-chloroform partition. This fraction was further refined by three successive partitions using hexane, carbon tetrachloride and chloroform VS. 10, 25 and 35% water in methanol, respectively. The bioactivity was localized in the carbon tetrachloride and chloroform phases. Chromatography of these materials through Sephadex LH-20 with methanol yielded in each case an orange colored biologically active fraction. Rechromatography of this colored material through silica gel using acetone-hexane mixtures as eluant yielded, in order of elution, crystalline sinulariolide, dihydrosinularin and sinularin. Sinularin (I) melted at 150-152" (acetone-hexane),