The potential value of lithium as a bronchodilator has been evaluated by in vitro methods using guinea pig tracheal spirals and lung parenchymal strips. The use of twin spirals and strips prepared by splitting the tissues longitudinally into two equal halves has been used to minimize animal variations. The cumulative concentration-effect relationships of isoproterenol have been determined on these twin tissues contracted submaximally with histamine. The responses of the twin tissues did not significantly differ. The cumulative concentration-effect relationships of lithium on guinea pig tracheal spirals and lung parenchymal strips have been evaluated and compared with those of isoproterenol. Lithium showed a dose-dependent relaxation on both tissues. However, the potency of lithium to produce a relaxant effect was significantly lower than isoproterenol. The relaxing effect of lithium on parenchyma was significantly higher than that on the trachea. The lithium-induced inhibitory effect on the contractile responses of tracheal spirals and lung parenchymal strips to histamine before and after incubating the tissues with lithium for 15 min has been determined. Lithium significantly reduced the contractile effect of histamine on both tissues. These findings suggest a potential clinical applicability of lithium for treating airway hyperresponsiveness.