Shipboard antimicrobial screening of Caribbean sponges revealed that fresh methanol extracts of Ulosa sp. 1 inhibited the growth of S. aureus, B. subtilis, C. Albicans, and several strains of marine bacteria. Chromatography of the concentrated extract on either silica gel or florisil resulted in loss of the antimicrobial constituent. A solid having the antimicrobial activity of the crude extract was obtained by rapid extraction of the lyophilized sponge with 10% methanol in acetone, evaporation of the solvent, and trituration of the residue with hexane. The solid (2% dry weight) consisted of a 3:1 mixture of two closely related metabolites 1 and 2, which could not be separated by chromatography. When a methanolic solution of the metabolites was evaporated and redissolved, some insoluble polymer was formed. Consideration of the accumulated spectral data led to the suggestion that the diosphenols 1 and 2 were the most probable structures for the isomeric antibiotics. The two metabolites 1 and 2 account for the antimicrobial activity of the crude extract. Both acetates 3 and 4, the methyl ethers 5 and 6, and even the adducts 7 and 8 have mild antimicrobial activity.