Regional differences in the sensitivity of guinea-pig airways to cholinergic and beta-adrenoceptor stimulation as well as Schultz-Dale responses were studied in vitro. Carbachol and isoproterenol produced a 27% and 39% greater response, respectively, in the trachea as compared to the bronchus. Contractions to histamine in tracheal and bronchial tissues were significantly less than those evoked by carbachol (P less than 0.05); however, lung parenchymal strips did not show any difference in maximal contractility to these agonists. Responses to antigen in airways from sensitized guinea-pigs or responses to anaphylactic mediators, LTD4 and PGD2, in normal airways did not show any differences in maximum tissue contractility (trachea and bronchus). Among the airway tissues examined, lung parenchymal strips were more responsive to these mediators as compared to tracheal and bronchial tissues. Threshold and sub-threshold concentrations of LTD4 had no effect on tracheal and bronchial airway contractions to PGD2; however, PGD2-induced contractions of the lung parenchymal strip were significantly inhibited in the presence of LTD4 (P less than 0.0001). Our data suggest that: (1) considerable regional differences exist in the reactivity of guinea-pig airways; (2) the maximum responses of bronchial airways to cholinergic and beta-adrenergic stimuli appear less than that observed in the trachea; (3) small peripheral airways appear more responsive to some mediators of anaphylaxis than are the larger central airways. Therefore, it would appear that the trachea and bronchus are more responsive to cholinergic stimuli, while the lung parenchyma is more responsive to PGD2, LTD4 and also to in vitro anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)