The aim of this study was to determine the value of an increase in plasma atrial natriuretic peptide (ANP) concentrations during submaximal exercise as a predictor of return of sinus rhythm (SR), and of its maintenance over a period of 6 months after cardioversion (CV) of chronic atrial fibrillation (AF). The study group included 42 patients with AF (mean duration 7 +/- 7 months) and a controlled ventricular rate. They underwent submaximal exercise testing 24 hours before CV. Blood samples were collected at rest and at peak of exercise for measurement of plasma ANP concentrations. Thirty-five of 42 patients were successfully cardioverted to SR. At 6 months, 23 patients remained in SR, while 12 had recurrence of AF. The plasma ANP concentrations before CV increased insignificantly during exercise in patients with unsuccessful CV or with recurrence of AF (60.8 +/- 17.3 pg/mL to 64 +/- 13.5 pg/mL, NS). The mean increase in plasma ANP concentration during exercise was significantly greater in the 23 patients who remained in SR than in the 19 patients unsuccessfully cardioverted or with recurrence of AF (17.5 +/- 7.6 pg/mL vs 5.8 +/- 4.5 pg/mL, P < 0.01). In multivariate logistic regression analysis, an increase in ANP plasma concentration was independently associated with successful CV and maintenance of SR up to 6 months of observation. In patients with chronic AF an exercise-induced increase in ANP concentration predicts successful CV and maintenance of SR.