Background: We examined whether and to what degree long-term angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 (AT1)-receptor blockade, or combined inhibition in developing congestive heart failure (CHF) alter myocardial interstitial bradykinin (BF) levels. Methods and Results: Pigs (27–30 kg) underwent rapid pacing–induced CHF (240 bpm, 3 weeks; n = 10); pacing CHF with concomitant ACE inhibition (benezaprilat, 3.75 mg/day; n = 10); pacing CHF and concomitant AT1-receptor blockade (valsartan, 60 mg/day; n = 10); pacing CHF and combined inhibition (benezaprilat/valsartan, 1.87/60 mg/day, respectively; n = 10); or served as controls (no pacing, no treatment; n = 10). Steady-state myocardial interstitial BK levels were quantitated by microdialysis. Cardiac output decreased to 1.95 ± 0.18 L/min in pacing CHF compared with control (3.78 ± 0.38; P <.05). Cardiac output increased from untreated CHF values with concomitant ACE inhibition (3.91 ± 0.27 L/min), AT1-receptor blockade (3.30 ± 0.41 L/min), or combined ACE/AT1-receptor inhibition (4.13 ± 0.32 L/min; all P <.05 v CHF). With pacing CHF, myocardial interstitial BK levels were reduced by approximately 50% from control values and were normalized in the ACE inhibition and combined inhibition groups. Conclusions: Long-term ACE inhibition increases myocardial interstitial BK levels with CHF; addition of AT1-receptor blockade does not seem to abrogate these effects.