Isolated systolic hypertension (ISH)--i.e. high systolic pressure with nonhypertensive (less than 90 mmHg) diastolic pressure--is a recognized risk factor for cardiovascular disease among individuals in the age group 60 years and above. This observation suggests that antihypertensive treatment might be beneficial. Results of the Systolic Hypertension in the Elderly Program Pilot Study (SHEP-PS) indicated the feasibility of a full-scale clinical trial on the efficacy of drug treatment of ISH. The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, double-blind, placebo-controlled clinical trial with the primary objective of assessing the effect of drug treatment of ISH--systolic pressure 160-219 mmHg and diastolic pressure less than 90--on occurrence of fatal and nonfatal stroke. This multicenter clinical trial has a sample size of 4736 participants, with high statistical power to detect a reduction of 32% or more in the study's primary end point during the 4-6 year period of treatment and follow-up. Low dosage chlorthalidone is the main study drug. Further features of the design of SHEP and the trial's organization are described.