ObjectiveThis long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo.Methods:One hundred and twelve older (±60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up.Results:At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (±SD) averaged 176±12/86±7 mmHg and 24-h SBP/DBP 151 ± 15/81 ± 10mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6±15.9 (P<0.001)/1.4±7.4 (P=0.06)mmHg and 24-h SBP by 2.4±10.7mmHg (PConclusions:These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomano-metry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.