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To investigate whether a clinic-ambulatory blood pressure difference persists with time under active drug treatment or placebo and to determine whether and how it interferes with the evaluation of the efficacy of antihypertensive treatment.In 382 mild or moderate essential hypertensive patients (mean age±SD 51.5 ± 9.2 years) clinic and ambulatory (SpaceLabs 90207 device) blood pressures were measured twice, under baseline conditions and after 4-8 weeks of antihypertensive treatment by calcium antagonists or angiotensin converting enzyme inhibitors (n=266) or of placebo administration (n=116). In each patient the difference between clinic and daytime average blood pressure was taken as a surrogate measure of the magnitude of the 'white-coat effect', separately for systolic and diastolic blood pressures. The changes in this difference induced by treatment and by placebo and the relationship between the blood pressure changes induced by drug treatment and by placebo and the magnitude of the difference before and during treatment or placebo, respectively, were computed.Before drug treatment, the difference was 16.6 ±13.6 and 10.1 ± 7.9 mmHg for systolic and diastolic blood pressures, respectively. During treatment the corresponding values were 11.9±14.2 and 6.8±9.2mmHg; both of the reductions were statistically significant Both for systolic and for diastolic blood pressure, the reduction in clinic blood pressure caused by treatment was directly related to the clinic-ambulatory difference before treatment, but inversely related to the magnitude of that difference persisting during treatment. The clinic-ambulatory blood pressure difference observed before placebo was attenuated during placebo, the magnitude of the attenuation being similar to that found under drug treatment. No significant difference between clinic and daytime average heart rate was ever observed before and during active treatment or placebo.A considerable clinic-ambulatory blood pressure difference persists during several weeks of antihypertensive treatment, but its magnitude is significantly attenuated. This leads to an overestimation of the effectiveness of antihypertensive treatment when this is assessed by clinic blood pressure measurements only. This overestimation is greater in subjects with an initially greater difference because in these subjects the subsequent attenuation is greater. Because similar phenomena are observed with placebo, the attenuation in the difference during drug treatment is likely to reflect merely habituation to clinic blood pressure measurements with time.