Long-term angiotensin-converting enzyme (ACE) inhibition in the spontaneously hypertensive rat (SHR) resets pressure natriuresis and shifts the relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) to lower levels of arterial pressure. These effects persist after withdrawal of treatment. The purpose of this study was to determine the effect of short- and long-term ACE inhibition on medullary blood flow (MBF). Enalapril (25 mg · kg¹ · day¹ in drinking water) was given to male SHR from 4 to 14 wk of age. Four weeks after stopping treatment, we measured MBF over a wide range of RAP using laser-Doppler flowmetry in anesthetized rats. Additional rats, either untreated or previously treated for 10 wk, received 3-day enalapril treatment just before the experiment. MAP (mmHg ± SE) was 178 ± 6 (n = 8), 134 ± 6 (n = 8), 138 ± 5 (n = 9), and 111 ± 6 mmHg (n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. Total renal blood flow for the groups receiving 3-day treatment was significantly higher when compared with that in rats with an intact renin-angiotensin system. Three-day treatment had no effect on the relationship between RAP and RIHP, whereas that in rats receiving 10-wk treatment was shifted to lower levels of RAP by ~30 mmHg. Both 10-wk and 3-day treatment independently increased the slope of the RAP versus MBF relationship at values of RAP > 100 mmHg. The slopes in perfusion units/mmHg were 0.12 ± 0.01 (n = 8), 0.26 ± 0.01 (n = 8), 0.27 ± 0.01 (n = 9), and 0.30 ± 0.02 (n = 9) for the untreated, 3 day, 10 wk, and 10 wk + 3 day groups, respectively. These results indicate that the effect of short-term and the persistent effect of long-term enalapril alter renal medullary hemodynamics in a way that may contribute to the resetting of the pressure-natriuresis relationship in treated rats.