OBJECTIVE We tested the hypothesis that beat-to-beat changes in haemodynamics during atrial fibrillation include an effect of each preceding R-R interval through the interval-strength relationship (mechanical restitution). BACKGROUND The variation in stroke volume and pulse pressure characteristic of atrial fibrillation is usually ascribed to time dependent ventricular filling. METHODS We measured the maximum rate of rise of left ventricular pressure (LVdP/dtmax), and aortic blood velocity and its integral in patients with atrial fibrillation undergoing cardiac catheterisation. The contractile response of isometric human myocardial trabeculae to sequences of atrial fibrillation was also studied, using the recorded ECGs as stimuli. The trabeculae were obtained from the resected right ventricular outflow tracts of patients with Fallot's tetralogy undergoing operative correction. RESULTS Beat-to-beat variations in contractile function during atrial fibrillation in the patients were recorded as LVdP/dtmax and left ventricular ejection (ascending aortic) velocity integral (proportional to stroke volume). Both these indices correlated well with the response to the same ECG (R wave) sequences in the isometric model measured as the maximum rate of rise of force, dF/dtmax, r = 0.72 to 0.81, p, 0.0001. When short pre-preceding intervals were excluded (minimizing the effect of post-extrasystolic potentiation), these variables showed a positive curvilinear relationship to preceding interval typical of mechanical restitution. CONCLUSIONS Mechanical restitution, which causes beat-to-beat changes in inotropic state, accounts in part for the changes in stroke volume in atrial fibrillation.