Felodipine is a new calcium antagonist with a high degree of vascular selectivity. Its potential role in the treatment of congestive heart failure was examined in short and long term oral studies. Short term felodipine 5 to 15 mg in 11 patients increased (p less than 0.001) cardiac index (from 2.1 +/- 0.1 to 3.3 +/- 0.2 L/min/m2), and reduced systemic resistance (from 26 +/- 2 to 12 +/- 2 units) and left ventricular end-diastolic pressure (from 26 +/- 2 to 13 +/- 2mm Hg) without affecting heart rate. Left ventricular max dp/dt did not change, but max dp/dt/p increased from 19 +/- 1 to 24 +/- 1 sec-1 (p less than 0.001). Left ventricular unloading was reflected by a shift in the end-systolic pressure-dimension relationship downwards and to the left. Myocardial oxygen supply to demand ratio improved significantly; coronary flow increased from 141 +/- 11 to 176 +/- 15 ml/min and myocardial oxygen consumption fell from 18 +/- 2 to 14 +/- 1 ml/min (p less than 0.05). Long term therapy with felodipine 30 mg daily in 10 patients improved treadmill exercise tolerance after 4 weeks by 24% (p less than 0.001). Stroke index at submaximal exercise increased from 37 +/- 3 to 47 +/- 2 ml/beat/m2 (p less than 0.001). Pulmonary capillary wedge pressure fell significantly (22 +/- 5 to 10 +/- 3mm Hg), as did arteriovenous oxygen difference (12.7 +/- 0.9 to 9.7 +/- 0.6 vols/100ml). Importantly, these beneficial effects with felodipine were sustained during 4 weeks' therapy without evidence of tachyphylaxis. These data indicate that the selective vasodilator properties of felodipine may extend the clinical application of calcium antagonists to include the management of heart failure.