Drugs known to interact with Na+ channels were compared as antagonists of Ca2+-induced contractions of K+-depolarized taenia preparations from guinea-pig caecum. Tetracaine (apparent pA2 5.3 +/- 0.2), quinidine (5.2 +/- 0.1) quinine (5.1 +/- 0.1), d-propranolol (4.7 +/- 0.1), 1-propranolol (4.7 +/- 0.1), lignocaine (4.0 +/- 0.1) and procaine (3.6 +/- 0.1) displaced cumulative concentration-response curves to Ca2+ to the right without depression the maximal response. The slopes of Arunlakshana and Schild plots were close to unity for quinidine, quinine, lignocaine and procaine. These drugs relaxed the established Ca2+-induced contractions rapidly and thus the effects of these drugs resembled the effects of low concentrations of verapamil. However, the effects of the local anaesthetics were increased in the presence of sodium salicylate (5-10 mM) which increases the negative surface charge. In contrast the effects of verapamil were decreased by salicylate. Veratridine (10-100 microM), which activates Na+ channels, had only depressant effects on Ca2+-induced contractions. Thus, drugs acting on Na+ channels can also interact with Ca2+ channels but there are qualitative as well as quantitative differences between the effects of these drugs and those of drugs such as verapamil. These findings indicate different mechanisms of action for the inhibition of Ca2+-induced contractions by local anaesthetics and verapamil.