An antimalarial macrocyclic polylactone, menisporopsin A (1), was isolated from a cell extract of the seed fungus Menisporopsis theobromae. The structure of 1 was elucidated on the basis of spectroscopic analysis and chemical transformations, with the absolute configuration established by application of the modified Mosher method and by using chiral HPLC. Menisporopsin A (1) possesses an unprecedented residue, 2,4-dihydroxy-6-(2,4-dihydroxy-n-pentyl)benzoic acid. This compound exhibited antimalarial activity, with an IC(50) value of 4.0 microg mL(-1), and antimycobacterial activity (MIC value of 50 microg mL(-1)).