Vasodilators, such as nitroglycerin, have been widely used in the treatment of acute and chronic heart failure for therapeutic manipulation of the venous and arterial circulations to improve left ventricular function. We have tested the efficacy of a new formulation for sustained release buccal delivery of nitroglycerin (biological life 5-6 hr) in 21 patients with severe congestive heart failure due to ischaemic cardiomyopathy using maximal treadmill exercise testing and radionuclide angiography. A single-blind placebo-controlled acute and an open chronic phase (4 weeks) of treatment were employed. The mean dose was 23.4 mg daily, and clinical assessment suggested significant improvement in 15 patients. The mean ejection fraction (placebo) of 14.1% +/- 1.6 SEM increased to 19.1% +/- 1.7 (acute) and to 21.6% +/- 1.7 (chronic treatment) (P less than 0.001; n = 16). The mean exercise time increased from 3.02 +/- 0.4 min (basal) to 5.95 +/- 0.6 min (chronic) (P less than 0.001). Segmental wall motion abnormality was shown to improve after treatment for 4 weeks. There were no major side effects. Nine patients were reassessed after 24 weeks on the same regimen; exercise time and left ventricular ejection fraction were similar to the 4-week period, thus demonstrating a sustained improvement in cardiac function and functional capacity. A worthwhile functional and objective haemodynamic improvement was demonstrated in these patients with severe chronic congestive heart failure. This mode of treatment may have useful therapeutic value in the management of patients with a wide range of ischaemic heart failure.