The combined CH(2)Cl(2) and MeOH crude extract of a new species of the marine sponge Dysidea, collected in Northern Australia was found to inhibit the binding of [I125] interleukin-8 [IL-8] to the human recombinant IL-8 receptor type A at 500 microg/mL. Bioassay-guided fractionation led to the isolation of three new polyoxygenated sterols 3, 4, and 5. Their structures were assigned on the basis of 1D and 2D NMR experiments, and relative stereochemistries were established by ROESY correlations and analysis of coupling constants. The IC(50) values for inhibition of IL-8Ra for sterols 3, 4, and 5 were 20, 5.5, and 4.5 microM, respectively.