Pharmacologic studies in hypertension often describe blood pressure (BP) reductions in placebo control groups. This placebo effect is currently debated, as it seems to be related to BP measurement methods and as a regression to the mean phenomenon may lead to misinterpretation. Furthermore, data on pulse pressure are lacking. This study was designed to evaluate the placebo effect on BP and to differentiate it from regression to the mean. According to a crossover design, 26 mild-to-moderate hypertensive patients who were treated with placebo or given no treatment were followed-up for 1 month. Clinic and ambulatory BP was assessed at baseline and at the end of each 1-month period. Placebo administration resulted in significant reductions in clinic systolic, diastolic, and mean BP (P < .01), ambulatory 24-h SBP (P < .05), and daytime systolic, diastolic, and mean BP (P < .01, P < .05, P < .01, respectively). No significant differences were noted for pulse pressure and heart rate or between BP values measured at baseline and after 1 month without treatment. Despite a significant correlation between changes in clinic and ambulatory BP, the scatter of individual data suggests that the placebo response observed with one method cannot be systematically extrapolated to the other method. This study conclusively shows the effect of placebo in mild-to-moderate hypertension on both clinic and ambulatory systolic, diastolic, and mean BP, in which it has been shown to differ from the regression to the mean phenomenon. This effect was not observed for pulse pressure or heart rate.