Two new antifungal and cytostatic macrolides, phorboxazoles A (1) and B (2), have been isolated from the Indian Ocean marine sponge Phorbas sp. Structural assignment was accomplished through extensive 2D NMR spectroscopy including COSY, RCT, HMQC, and HMBC. The complete relative stereochemistry about the macrolide ring and solution conformation of 1 were established from analysis of ROESY experiments. Phorboxazoles A and B exhibit in vitro antifungal activity against Candida albicans at 0.1 mu g/disk and extraordinary cytostatic activity (mean GI(50) < 7.9 x 10(-10) M in the National Cancer Institute’s 60 tumor cell line panel).