Antarctic sponges are commonly fouled by diatoms, sometimes so heavily as to occlude pores employed in filter feeding and respiration. This fouling becomes heavier during the annual summer microalgal bloom. Polar and non-polar extracts of eight species of marine sponges from McMurdo Sound, Antarctica were assayed for cytotoxicity against sympatric fouling diatoms. To identify compounds potentially released by sponges as defenses against diatom biofouling, only fractions of crude extracts that were soluble in seawater or 2% methanol in seawater were assayed. Significant bioactivity was present in seven of the eight species. Both Mycale acerata and Homaxinella balfourensis displayed moderate levels of defense against diatoms even though they are not or are only weakly chemically defended against bacteria and predators. Calyx acuarius extracts, which do have antipredator and antibacterial effects, had no effect on diatoms except at levels many fold higher than present in the intact animal. These results strongly suggest some level of specificity for chemical defenses against diatom fouling in antarctic sponges.