The aim of this 3-month double-blind, placebo-controlled, multicenter trial was to evaluate the clinical efficacy and safety of perindopril, a new long-acting angiotensin-converting enzyme inhibitor in the second-line treatment of mild to moderate chronic congestive heart failure. After a run-in period of at least 14 days, 125 patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy were randomized to perindopril, 2 mg (n = 61), or placebo (n = 64), once daily. Assessment was at 2-week intervals for the first month and then monthly for the 2 following months. After 2 weeks, active treatment was increased to perindopril, 4 mg once daily, if systolic blood pressure was 100 mm Hg or greater. Apart from sex, the two groups were homogeneous before treatment. As shown by the end-point analysis, the increase in exercise time was greater with perindopril than with placebo for both the ergometric bicycle (+111 +/- 21 versus +16 +/- 20 seconds; p = 0.002) and the treadmill (+171 +/- 39 versus +36 +/- 42 seconds; p = 0.024). Compared with placebo, this increase in exercise tolerance with perindopril was accompanied by an improvement in New York Heart Association functional class (p = 0.009), overall heart failure severity score (p < 0.001), and cardiothoracic ratio (p = 0.05). Of the 12 withdrawals from the study, seven were attributed to adverse events, two in the perindopril group and five, including one death, in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)