To determine if mediator release would occur in the airways of human subjects after exposure to a hyperosmolar stimulus, we challenged isolated airway segments in vivo with 900 mosmol sodium chloride using a specially designed double-balloon catheter. In order to determine if differences in mediator concentrations correlated with airway responsiveness or with atopy, we studied 3 separate groups: 6 atopic, asthmatic subjects; 6 atopic, nonasthmatic subjects; and 6 nonatopic, nonasthmatic normal subjects. In addition, to determine if the presence of the catheter itself was a stimulus, we studied 6 atopic, asthmatic subjects after exposure to isotonic sodium chloride alone (sham exposure). Lavage specimens were assayed for PGD2, PGF2 alpha, PGE2, TxB2, LTC4, and LTB4 by radioimmunoassay and for histamine by the modified single isotope enzymatic assay. The histamine concentration of the baseline lavage samples (bronchoalveolar lavage and isolated airway segment lavage) for the subjects with asthma were significantly greater than for the atopic or normal subjects (p less than 0.05). There was a significant negative correlation between histamine concentration in the lavage samples and the airway responsiveness of the subjects (r = -0.53, p less than 0.0001). There was a marked correlation among the concentrations of histamine, PGD2, PGF2 alpha, and TxB2 in all the lavage fluids for the subjects with asthma (p less than 0.03 for all comparisons and p less than 0.0001 for overall concordance). As a result of hyperosmolar challenge, there was a significant increase in the concentration of histamine, PGD2, and PGF2 alpha in the subjects with asthma.(ABSTRACT TRUNCATED AT 250 WORDS)