Atrial natriuretic peptide (ANP) has been reported to have protective effects against methacholine-induced bronchoconstriction in asthmatics. The aim of the study was to evaluate the relationship between plasma ANP levels and bronchial responsiveness to methacholine in patients with mitral stenosis. In 12 patients with moderate mitral stenosis, age 35-58 years, 9 female, 8 in NYHA class 2, 4 in NYHA class 3 for symptoms, plasma ANP and bronchial threshold to methacholine (PD20FEV1) were determined. The same measurements were performed in 10 asthmatic patients, hyperresponsive to methacholine, and in 10 normal subjects, nonresponsive to methacholine. Mean +/- SE plasma ANP levels were significantly higher in patients with mitral stenosis in comparison with asthmatics and normals (159 +/- 41.8, 7.3 +/- 0.98, 7.6 +/- 1.3, respectively, p < 0.01). In patients with mitral stenosis there was a significant relationship between plasma ANP and PD20FEV1 (r = 0.81, p < 0.01). No relationship was found between ANP and PD20FEV1 in asthmatics. In conclusion, in patients with mitral stenosis ANP seems to play a protective role against bronchial hyperresponsiveness to methacholine.