A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.