During a 12-week, multicenter study to evaluate the efficacy and safety of lisinopril and hydrochlorothiazide (HCTZ) for the treatment of obesity-related hypertension, ambulatory blood pressure (ABP) monitoring was performed both at baseline and at study completion in 124 patients. Patients were randomized to three groups: placebo, lisinopril (10, 20, or 40 mg/day), or HCTZ (12.5, 25, or 50 mg/day). All groups were matched with regard to sex, race, age, body mass index, and waist/hip ratio. The primary analysis of ABP data revealed that both lisinopril and HCTZ effectively lowered mean 24-h systolic (SBP) and diastolic (DBP) blood pressure compared with placebo, (mean change from baseline SBP/DBP: -12.0/-8.2, -10.6/-5.5, and -0.3/-0.5 mm Hg, respectively); however, lisinopril lowered DBP better than HCTZ (P < .05). Secondary analyses of groups revealed that men responded better to lisinopril than HCTZ (-11.9/-7.3 v -6.6/-3.5 mm Hg, respectively), whereas women responded well to both drugs. White patients responded better to lisinopril than HCTZ, whereas black patients showed a significant response to HCTZ only. Response to treatment was also influenced by patient classification of 24-h blood pressure profiles, ie, "dipper" or "nondipper." Overall, the majority of obese hypertensives were nondippers. Nondippers (n = 82) responded well to both drugs (-10.4/-6.9 v -12.5/-5.7 mm Hg, P < .05 v placebo), whereas dippers (n = 42) responded to lisinopril (-11.7/ -9.4 mm Hg, P < .05 v placebo and HCTZ), but not HCTZ (-5.6/-4.1 mm Hg, P = NS v placebo). Results of 24-h ABP data show that both lisinopril and HCTZ are effective therapies for obesity-related hypertension and that response to treatment is influenced by sex, race, and dipper/nondipper status.