BACKGROUND Any hypertensive patient may be found to have associated lung disease. The response of high blood pressure to specific antihypertensive agents in this category is still unknown. Thus, a group of 76 consecutive patients with mild-to-moderate hypertension and chronic obstructive pulmonary disease (COPD) were selected to participate in a clinical antihypertensive trial to define the roles of lisinopril, nifedipine and conventional therapy, and their impact on the renin-antiotensin system (RAS). METHODS After a two-week placebo period, patients were randomly assigned to a regimen of one of three main treatment strategies: (A) lisinopril with or without diuretics; (B) nifedipine with or without diuretics; or (C) diuretics with or without conventional vasodilators (sorbitrate and hydralazine) or selective beta-blockers. The drug doses were titrated to a goal of less than 90 mmHg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS After one year of follow-up, only 66 patients had completed the study. All high blood pressure was significantly reduced by the three regimens (p < 0.005), but no significant difference in blood pressure control by any individual regimen was noted. Double product also showed the similar trend. Therapy A achieved the best reduction of double product among three regimens, but statis tieally insignificant. Furthermore therapy A suppressed the RAS, whereas therapies B and C might activate this system. Concomitantly, therapy A also had significant favorable effects on metabolic responses in contrast to therapy C. Therapy B revealed a neutral effect on such responses. CONCLUSIONS These data indicated that these three main strategies could provide significant antihypertensive efficacy for blood pressure control in patients with hypertension and COPD. For preventive strategy, therapy A may provide more advantageous effects than therapy C. A long-term double-blind trial including more subjects is warranted to identify the true advantages of therapy A in reduction or major cardiovascular and respiratory events.