Apicularen A (Api A) was recently isolated from Chondromyces sp. as a potent antitumor agent. Because of its unique chemical structure, a macrolide with a highly unsaturated amide side chain, and potent growth inhibitory effect in various cancer cell lines, Api A is currently in clinical trial for cancer therapy. In the present study, the effect of Api A on in vitro angiogenesis of bovine aortic endothelial cells (BAECS) was investigated. Api A potently inhibited the proliferation of BAECS in a dose-dependent manner. Treatment of the endothelial cells with up to 10 ng/ml of the compound did not show any cytotoxicity. In addition, it inhibited basic fibroblast growth factor (bFGF)-induced invasion and capillary tube formation of BAECS at concentrations of 2-5 ng/ml. These results, therefore, demonstrate that Apl A is a novel antiangiogenic agent and may suppress the growth of tumors, at least in part, by the inhibition of neovascularization.