Three new furan derivatives, plakorsins A-C (6-8), together with a new fatty acid, plakortic acid (9), have been isolated from the Taiwanese marine sponge Plakortis simplex in addition to the known metabolites chondrillin (1), 6-epi-chondrillin (2), 2-oxo-2,5-dihydrofuran-5-acetic acid methyl ester (methyl 1,4-epoxy-1-oxo-2-hexenoate) (3), dimethyl beta-ketoadipate (4), and the monomethyl ester of cis,cis-muconic acid (5). The structures of these compounds were established mainly on the basis of spectral data and chemical methods. Biological studies revealed that compound 7 exhibited cytotoxic activity against COLO-250 and KB-16 cells, and compound 1 is active against KB-16 cells.