Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP), and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P<0.05), at peak effect, but LVFP was no longer significantly lower by 20 minutes after NTG. After CHIS, LVFP fell significantly within five minutes, reached a peak reduction of 8.6 mm Hg (32.7%, P<0.01) at 15 minutes, and remained significantly lower through three hours. Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.