Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD(20) methacholine (PD(20(M))), PD(15) hypertonic saline (PD(15(HS))) and their dose-response slopes (DRS(M) and DRS(HS)) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD(15(HS)) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3-123.5, p < 0.05), and time to BOS was significantly and negatively related to DRS(HS) (r = -0.5, p < 0.05) - that is, the greater the response, the shorter the time to BOS. Interestingly, DRS(HS) correlated positively with recipient:donor total lung capacity ratio (r = 0.5, p < 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development.