Two new 10-membered lactones, namely, multiplolides A (1) and B (2), were isolated from the broth extract of the fungus Xylaria multiplex BCC 1111. Chemical structures of 1 and 2 were elucidated on the basis of their spectral data. Multiplolides A (1) and B (2) exhibited antifungal activity against Candida albicans with IC(50) values of 7 and 2 microg/mL, respectively. Both 1 and 2 were inactive in the screening systems toward the malarial parasite Plasmodium falciparum (at 20 microg/mL) and were not cytotoxic to BC-1 and KB cell lines (at 20 microg/mL).