OBJECTIVE: To study the effect of transdermal scopolamine on heart rate variability, baroreflex sensitivity, and exercise performance in patients with heart failure and age matched healthy volunteers. DESIGN: Double blind, randomised, placebo controlled, crossover study. PATIENTS: 16 patients with chronic, stable heart failure due to ischaemic cardiomyopathy (mean (SEM) age 58 (2) years; mean (SEM) radionuclide left ventricular ejection fraction 28 (2)%; New York Heart Association class II-III) and eight age matched healthy controls. INTERVENTION: Transdermal scopolamine (500 micrograms delivered over 72 h) or a placebo patch was administered for 48 h. MAIN OUTCOME MEASURES: Indices of tonic and reflex cardiac vagal activity and exercise performance. RESULTS: In both groups scopolamine produced a reduction in the 24 h average heart rate and an increase in the time domain measures of heart rate variability. Both the incidence and severity of ventricular arrhythmias remained unchanged. Baroreflex sensitivity, evaluated by the phenylephrine technique, increased significantly (P < 0.001) with scopolamine in patients with heart failure (6.22 (2.81) ms/mm Hg) and in healthy volunteers (5.97 (2.20) ms/mm Hg) as did the amplitude of respiratory sinus arrhythmia, computed by autoregressive spectral analysis of 10 min electrocardiographic recordings (319.9 (123.5) and 657.3 (126.6) ms2 respectively, P < 0.001). While exercise performance did not change, heart rate at submaximal exercise was significantly reduced by scopolamine in each group. CONCLUSIONS: In patients with mild to moderate heart failure low doses of scopolamine increased tonic and reflex cardiac vagal activity. This was achieved without affecting exercise tolerance or the incidence and severity of ventricular arrhythmias.