Removal of the epithelial layer of rat tracheal tissue did not affect the methacholine-induced contraction of the tracheal smooth muscle, but attenuated the (-)-isoprenaline induced relaxation (expressed as percentage of the methacholine contraction). In this way the epithelial layer seemed to play a role in the maintenance of an autonomic balance between sympathetic and parasympathetic receptor responses. Incubation of rat tracheal tissue with cumene hydroperoxide (3 x 10(-5)-10(-3) M) resulted in a dose-dependent destruction and (partial) removal of the epithelial layer. Cumene hydroperoxide diminished muscarinic receptor responses of the rat trachea. Moreover, the autonomic balance between muscarinic and beta-adrenoceptor responses was affected. The effects of cumene hydroperoxide on receptor responses were more pronounced after epithelium removal. The protective role of the epithelial layer of pulmonary tissue against oxidative stress has therefore been emphasized.