Previous studies have shown inconsistent results of the effect of verapamil and nifedipine on airway reactivity. This study was undertaken to determine and compare their effects on the activity of airway muscarinic receptors by contraction experiments and by radioligand receptor binding assays. We found that verapamil (10(-5)-10(-4) M) reduced contraction at rat tracheal muscle to methacholine, a finding consistent with its inhibition on binding of (3H)QNB to bovine tracheal muscle membranes. Unlike verapamil, nifedipine (10(-5)-3 X 10(-5) M) inhibited neither methacholine response nor (3H)QNB binding. Verapamil but not nifedipine decreased the affinity of binding sites. Neither of them affected the concentration of (3H)QNB binding sites. We conclude that the effect of verapamil on airway muscarinic receptor binding sites differs qualitatively from that of nifedipine, and suggests that its effect on the binding sites could account for the inhibitory action of verapamil on airway muscarinic response.