Five of 11 normotensive patients with congestive heart failure responded to an infusion of the specific angiotensin II antagonist, saralasin, by reducing systemic vascular resistance from 2274 +/- 418 to 1690 +/- 351 dynes/sec/cm-5 (mean +/- standard error). This decrease was accompanied by a reduction in left ventricular filling pressure from 19.4 +/- 5.9 to 11.6 +/- 4.0 mm Hg, an increase in cardiac index from 2.2 +/- 0.4 to 2.7 +/- 0.4 l/min/m2 and a decrease in mean arterial pressure from 95 +/- 9.8 to 86 /+- 8.6 mm Hg. In the other 6 patients with congestive heart failure and in 4 controls, saralasin produced either no change or slight increases in systemic vascular resistance. Plasma renin activity did not differentiate responders from non-respnders. Specific inhibition of angiotensin may provide a means for reducing inappropriately high peripheral resistance in some patients with congestive heart failure.