The anti-histaminic principle in green-lipped mussel (Perna canaliculus) was isolated by a combination of countercurrent distribution and column chromatographies on silica gel and Sephadex LH-20, and identified as lysolecithin. There is evidence that the mussel may be of benefit in the treatment of inflammatory joint disease, including allergy, with moderate anti-inflammatory activity and an inhibitor of prostaglandin biosynthesis reported, but no detailed chemical studies to identify the active principle had yet been reported. The present study describes the isolation of an anti-histaminic principle from the mussel. Anti-histaminic activity was screened using the contractile response of isolated guinea pig ileum to histamine. Isolation was achieved via countercurrent distribution (using solvent systems n-BuOH:H₂O:AcOH = 5:4:1, CHCl₃:MeOH:H₂O = 5:5:3, and C₆H₆:CHCl₃:MeOH:H₂O = 15:15:23:7), silica gel column chromatography, and Sephadex LH-20 column chromatography. The purified substance was identified as lysolecithin based on thin layer chromatography (matching standard lysolecithin in two solvent systems), proton nuclear magnetic resonance (showing aliphatic acid ester, hydroxyl, and N-trimethyl moieties), infrared spectroscopy (confirming hydroxyl and ester groups), elemental analysis (C:N:P ratio ~24:1:1), and gas chromatography of fatty acid methyl esters (major fatty acids C₁₆:₀, 80.2%; C₁₈:₀, 12.0%). The natural lysolecithin exhibited anti-histaminic activity equivalent to an authentic sample, inhibited the contractile response of guinea pig ileum to nicotine, was unstable in alkaline medium but stable in acid and heat, and reduced carrageenan-induced hind paw edema in rats at 3 hours post-treatment. Attempts to isolate other biologically active principles from the mussel are in progress.