To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation.