The immunogenicity of a pore-forming polypeptide, equinatoxin II, from the sea anemone Actinia equina was studied after attenuation of the toxin's lethal and cytolytic activity by autologous polar lipids. In BALB/c mice, the lipid-inactivated toxin was used to raise specific antibodies and cellular immunity, resulting in in vivo protection. In vitro, haemolytic activity could be diminished by both normal and immune serum, the latter being more efficient. Purified specific IgG1 and IgG2 did not or only poorly neutralized the haemolytic activity, therefore implying the marked role of serum lipoproteins in the toxin attenuation. In response at the cellular level, equinatoxin II activated specific splenocytes. Increased concanavalin A stimulation of specific splenocytes was observed in the absence of antigen.