During our screening for microbial inhibitors of lipid droplet accumulation in macrophages, a new compound designated spylidone was isolated along with two structurally related known compounds, PF1052 and vermisporin, from the fermentation broth of Phoma sp. FKI-1840 by solvent extraction, silica gel column chromatography, ODS column chromatography and preparative HPLC. From the structure elucidation, spylidone has a spiro ring containing 2,4-pyrrolidinedione. Among the three compounds, only spylidone was found to inhibit lipid droplet accumulation in macrophages at 10ϳ50 mM without any cytotoxic effect.