The effects of diltiazem and 3 other Ca2+ antagonists (verapamil, nicardipine, bepridil) were studied on isolated guinea-pig tracheal preparations which were contracted with several agonists. Assessment of the contractile agonists was performed under physiological conditions as well as in Ca2+-depleted solutions. The order of potency of the contractile agonists was LTD4 greater than ACh greater than 5-HT greater than Hist greater than BaCl2 greater than TEA greater than KCl. The efficacy of the physiological agonists ACh, Hist and LTD4 was moderately depressed in Ca2+-free solutions while the responses to non-specific agonists and 5-HT were markedly reduced. Diltiazem and verapamil reduced basal tone at concentrations greater than or equal to 10(-4) M. Diltiazem displaced all agonist concentration-effect curves to the right. The four Ca2+ antagonists studied had a marked effect on non-physiological agonists as compared to that on physiological agents. Increasing Ca2+ concentration only partially reversed the inhibitory effect of diltiazem.