The action of the ichthyotoxic secretion of the Red Sea flatfish Pardachirus marmoratus and its derived toxin, pardaxin, was examined in the dogfish shark (Squalus acanthias). Pardaxin was more toxic when administered to the bathing medium than when injected into a dorsal artery and it transiently diminished the spiracular rate and caused a severe struggling response in the adult shark only when administered to the head region of the shark. Pardaxin caused a transient leakage to urea and sodium between the shark and the seawater. In the isolated perfused rectal gland pardaxin irreversibly reduced the rate of chloride secretion and concentration gradient of urea between perfusate and rectal gland fluid. In addition, ultrastructural studies on the rectal gland showed that ionic lanthanum penetrated the tight junctions and foci of cell necrosis were observed. These studies indicate that in shark the gills are the most probable target of the toxicity of pardaxin.