The renieramycin-producing sponge, Xestospongia sp., is a coral reef inhabitant occurring in the Gulf of Thailand. The distribution patterns of Xestospongia sp. and its association with other organisms were investigated, with results showing that the most frequently coexisting organisms were the massive coral, Porites lutea, and the colonial zooanthid, Palythoa caesia, but it also inhabited algal patches and dead coral rubble. The largest individuals of Xestospongia sp. were found growing on Pa. caesia while the smallest individuals were found on algal patches. The results also showed that concentrations of renieramycin M, the main alkaloid with highly potent cytotoxicity, extracted from this sponge differed significantly among sites (p < 0.05).