Potent anti-adherent activity was detected in fermentation extracts of microbial strain FO-5050. Active compounds designated macrosphelide A and B were isolated and the structure was determined to be 16-membered macrolide antibiotics possessing three ester bonds in the ring structure. Macrosphelide A dose-dependently inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC50, 3.5 microM); macrophelide B also inhibited HL-60 adhesion but to a lesser extent (IL50, 36 microM). Macrosphelide A did not show any antimicrobial and cytocidal activities at the concentration of 1000 micrograms/ml and 100 micrograms/ml, respectively.