Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium-free Krebs solution and tested with inhibitors of calcium channels. In calcium-free Krebs solution, the myotropic effects of substance P (10(-7) M), neurokinin A (3.10(-8) M), acetylcholine (2.10(-5) M), and histamine (2.10(-5) M) were reduced by 27-57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10(-8)-10(-6) M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10(-5)-10(-4) M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10(-6) M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage-operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.