Crude extracts of the coelenterate Aiptasia mutabilis (Anthozoa, Aiptasiidae) nematocysts have been tested for their cytotoxicity of Vero and HEp-2 cells monolayers. The results indicate that the nematocyte venom contains one or more toxins with an extremely powerful cytolytic activity. An extract containing the equivalent of as little as 0.6 nematocysts/AL is sufficient to induce significant cellular necrosis, and IC50 can be estimated to be ca. 2 nematocysts/AL on Vero cells. These values are 1–2 orders of magnitude lower than those reported so far for other sea anemone venoms. The extreme potency is accompanied by poor stability of the venom that is readily inactivated by moderate heat and by buffers at non-neutral pH values. The extract is unstable even when kept for short times at 4 8C, or after storage at 20 8C. Separation of crude venom by affinity chromatography on ConA-Sepharose allowed us to identify two main components with molecular masses of 95 and 31 kDa, respectively, as responsible for the cytolytic properties of A. mutabilis nematocyst extract.