Isometric tension responses of isolated porcine coronary artery rings were studied in the presence of concentrations of propranolol higher than those necessary to block effects mediated by beta-adrenergic receptors. Propranolol (50-300 microM) inhibited contractions induced by 30 mM KCl and by histamine, norepinephrine, and acetylcholine in a concentration-dependent, noncompetitive fashion. The (+) propranolol isomer and the racemic mixture were equipotent inhibitors of contraction. Propranolol inhibition was partly reversed by increased extracellular Ca++. These effects of propranolol thus appeared to be independent of beta-blockade and could be relevant to some of the drug's observed but still unexplained in vivo actions.