The spongeLissodendoryx isodictyalis is an odorous, encrusting, blue-gray sponge found on subtidal flats in North Carolina waters. The strong odor ofL. isodictyalis, coupled with the observation that it is rarely overgrown by fouling organisms, suggested that this sponge may produce metabolites with potent antifouling activity. Ethyl acetate extracts ofL. isodictyalis inhibit larval settlement of the barnacleBalanus amphitrite in laboratory assays at 10 ng/ml. Barnacle settlement bioassays of isolated preparative TLC fractions show thatL. isodictyalis produces at least two pungently scented, antifouling agents with EC50 values of less than 85 μg/ml and less than 250 μg/ml, respectively. The most potent agent inhibits settlement at or below a concentration of 400 ng/ml and kills approximately 25 % of settlement-stage barnacle larvae at 400 μg/ml. The other agent causes 100% mortality of larvae at concentrations greater than 400 μg/ml and inhibits settlement at approximately 40 μg/ml. These metabolites ofL. isodictyalis may inhibit overgrowth of the sponge in nature.