The relaxant effects of five organic calcium antagonists (nicardipine, diltiazem, PY 108068, verapamil and bepridil) on guinea-pig isolated trachea were tested against contractions induced by acetylcholine, histamine, 5-hydroxytryptamine, potassium chloride (KCl) and tetraethylammonium (TEA) in a medium containing the normal amount of calcium and against calcium dose-response curves in a calcium-free, potassium-enriched medium. These effects were compared with those of spasmolytic or specific acetylcholine or histamine antagonists. In contrast to the other drugs tested, organic calcium antagonists exerted a specific inhibitory effect on KCl- and TEA-induced contractions. Their degree of activity was in the order: nicardipine greater than diltiazem greater than PY 108068 greater than verapamil greater than bepridil. All calcium antagonists inhibited calcium dose-response curves at similar concentrations. Organic calcium antagonists therefore seem to exert a specific inhibitory effect on depolarizing agents in the guinea-pig isolated trachea, unlike other tissues, notably some vascular smooth muscles.