The effects of angiotensin-converting enzyme (ACE) inhibitors in high-output heart failure have not yet been well established. We evaluated the effects of lisinopril (3 mg/kg/day) on hemodynamics, neurohormones, and survival in 10-week-old spontaneously hypertensive rats (SHR) with aortocaval fistula. Sham-operated treated and untreated SHR served as controls. Cardiac output (CO) was determined by thermodilution method, and renal blood flow (RBF) was assessed by laser-Doppler flow-metry. In sham-operated SHR, 2-week treatment with lis-inopril decreased blood pressure (BP), left ventricular (LV) weight, and total peripheral resistance (TPR) (p < 0.01 each) and increased RBF and plasma renin activity (PRA) (both p < 0.05); CO and LV end-diastolic pressure (LVEDP) were unchanged. Fistula creation induced biventricular hypertrophy and high-output heart failure [increased LVEDP, CO, pulse pressure, and plasma norepinephrine (NE) and decreased RBF] with congestive signs (ascites, tachypnea). Lisinopril decreased LVEDP (p < 0.01), increased RBF, prolonged survival (both p < 0.05), and prevented ascites (0 vs. 46%) and increased PRA (p < 0.05) and attenuated the increase in plasma NE. Heart weight, BP, and CO were not affected by lisinopril. Thus, lisinopril ameliorated congestion and improved survival in SHR with fistula without compromising cardiorenal hemodynamics. Venous and renal dilatation and attenuation of vasoconstrictive systems may have contributed to the beneficial effects.