The hypothesis that antihypertensive drugs should be prescribed to elderly patients with isolated systolic hypertension is being addressed in at least 3 trials: the Systolic Hypertension in the Elderly Program (SHEP) in the United States, a trial in China, and the Syst-Eur study in Europe. The SHEP trial has recently reported its final morbidity and mortality results. This article summarizes the protocol of the European study. To be eligible for the Syst-Eur trial, patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized into active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/d), combined with enalapril (5-20 mg/d) and hydrochlorothiazide (12.5-25 mg/d), as necessary. The control group received matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the two treatment groups.