The effects of anesthetics on airway smooth muscle tone are important in the management of patients with asthma. In the present study we evaluated the effect of propofol and ketamine on isolated guinea-pig tracheal preparations mounted for recording isometric contractile force. In a concentration-dependent way both drugs produced 100% relaxation irrespective of whether tracheal tone was spontaneous or induced by carbachol, histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. The relaxant potency of propofol was dependent of the formulation of the drug used. Propofol showed an about 3 times higher potency when solubilized with hydroxypropyl-beta-cyclodextrin compared with an oil-in-water emulsion of the drug (Diprivan). Propofol had the greatest potency on tracheal preparations with spontaneous tone (EC50 = 4.0 +/- 0.9 microM). Ketamine preferentially relaxed contractions elicited by carbachol (EC50 = 120.8 +/- 5.2 microM) and had a lower potency than propofol when tone was spontaneous or induced by other tracheal spasmogens. Since propofol was a more effective tracheal relaxant in vitro than ketamine, the possibility that propofol, like ketamine, may inhibit bronchoconstriction during anesthesia should be studied further.