Amodiaquine (3.5 . 10(-7) mol/l), a 4-amino-quinoline antimalarial, increases the responses of the guinea-pig isolated ileum to direct (acetylcholine, histamine, barium, chloride), partially (5-hydroxytryptamine, PGE1 and F2 alpha) and totally (electrical stimulations, nicotine) indirect agonists. Moreover it reverses inhibitions of the electrical induced contractions by acetylcholine antagonists (atropine), acetylcholine release blocking agents (morphine, tetrodotoxin, procaine, noradrenaline) and prostaglandin synthesis inhibitors (indomethacin, ibuprofen, flufenamine acid, hydrocortisone). From 2.7 . 10(-6) mol/l, it induces dose-related tonic contractions which are totally and reversibly abolished by indomethacin as well as by the prostaglandin antagonist, polyphloretin phosphate, but not by atropine, morphine and tetrodotoxin. This indicates that amodiaquine exerts both a direct muscular non selective ileal sensitization to various agonists and, but at higher concentrations, a contractile effect apparently dependent on prostaglandin synthesis and release. At even higher concentrations (5.4 . 10(-6) mol/l) an effect of amodiaquine on acetylcholine release was demonstrated by the observation of phasic contractions inhibited by atropine, morphine and tetrodotoxin. These effects are different from those found by us with several other antimalarial compounds in the same preparation.