Purpose: The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Materials and methods: Forty patients with CHF [left ventricular ejection fraction (LVEF) < 45%; mean 33 +/- 7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from I-123-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. Results: After treatment, in patients receiving perindopril, TDS decreased from 39 +/- 10 to 34 +/- 9 (P < 0.01), H/M ratios increased from 1.62 +/- 0.27 to 1.76 +/- 0.29 (P < 0.01), WR decreased from 50 +/- 14% to 42 +/- 14% (P < 0.05) and plasma BNP concentrations decreased from 226 +/- 155 to 141 +/- 90 pg/ml (P < 0.0005). In addition, the LVEDV decreased from 180 +/- 30 to 161 +/- 30 ml (P < 0.05) and the LVESV decreased from 122 +/- 35 to 105 +/- 36 ml (P < 0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33 +/- 8% to 36 +/- 12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Conclusion: Plasma BNP concentrations, I-123-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF.