Arterial blood pressure rises at apnea termination, and there is increasing evidence that the sleep apnea-hypopnea syndrome (SAHS) is associated with daytime hypertension but no randomized controlled trial evidence of whether SAHS treatment reduces blood pressure exists. We, therefore, conducted a randomized placebo-controlled cross-over study of the effects of 4 wk of continuous positive airway pressure (CPAP) or oral placebo on 24-h blood pressure in 68 patients (55 males, 13 females; median apnea-hypopnea index [AHI], 35) not receiving hypotensive medication. Ambulatory blood pressure was recorded for the last 48 h of each treatment. Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) were also recorded. All patients were normotensive. There was a small decrease in 24-h diastolic blood pressure (placebo, 79.2 [SE 0.9] mm Hg; CPAP, 77.8 [SE 1.0] mm Hg; p = 0.04) with the greatest fall occurring between 2:00 A.M. and 9:59 A.M. The observed decrease in 24-h diastolic blood pressure was greater in two a priori groups, CPAP use > or = 3.5 h per night (81.5 [SE 1.2] mm Hg; 79.6 [SE 1.2] mm Hg; p = 0.03) and those with more than twenty 4% desaturations per hour (82.4 [SE 2.1] mm Hg; 77.4 [SE 2.1] mm Hg; p = 0.002). Systolic pressure also fell in the latter group (133.1 [SE 2.8] mm Hg; 129.1 [SE 2.1] mm Hg; p = 0.009). Desaturation frequency was the best predictor of diastolic blood pressure fall with CPAP (r = 0.38; p = 0.002). Both ESS and FOSQ domains improved. Thus, CPAP can reduce blood pressure in patients with SAHS, particularly in those with nocturnal oxygen desaturation, but the decrease is small.