The new polyketides leptosphaerins A-G (1-7) and the known compounds monodictysin B (8), 2-(2,6-dihydroxybenzoyl)-3-hydroxy-5-methylbenzoic acid (9), and 2-(2,6-dihydroxy-4-methylbenzoyl)-6-hydroxybenzoic acid (10) have been isolated from solid cultures of the ascomycete fungus Leptosphaeria sp. The absolute configurations of compounds 1, 2, and 6 were assigned using the modified Mosher method, whereas that of C-2 in 3 was determined via the circular dichroism data of the [Rh(2)(OCOCF(3))(4)] complex. Compound 7 showed antifungal activity against Aspergillus flavus.