BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.