The effect of epithelium removal on the responses of porcine airways to exogenously applied agonists and nerve stimulation was examined. Paired rings of third- (segmental), fourth- and fifth-order (subsegmental) bronchi, with and without epithelium, were placed in organ chambers in physiological salt solution (95% O2-5% CO2, 37 degrees C). Removal of the epithelium caused a leftward shift in the concentration-effect curve for acetylcholine (3rd and 4th order). A similar shift occurred for histamine (3rd and 5th order). The relaxation to isoproterenol was reduced by epithelium removal in a similar fashion in the three orders. Removal of the epithelium reduced the maximal response to KCl (3rd and 4th order) and acetylcholine (5th order). The peak response to nerve stimulation showed a significant rightward shift in the absence of epithelium. In fifth-order bronchi, tissues with epithelium showed a significantly greater degree of fade of the response to sustained electrical stimulation. Thus both epithelium-derived relaxing and contracting factors may be released in porcine airways.