The INternational VErapamil SR/trandolapril STudy (INVEST) will provide a large database of information. Proposed substudies for analysis include ambulatory blood pressure monitoring (ABPM), depression, genotyping, atrial fibrillation, electrocardiogram (ECG), echocardiography, renal dysfunction, diabetes, and cardiac care cost estimate. This paper reviews the design and status of several of the INVEST substudies. The ABPM substudy will obtain objective blood pressure recordings during daily life masked to both the patient and the investigator. Ambulatory blood pressure monitoring is an especially useful technology because of the role of nocturnal hypertension and circadian blood pressure irregularities in the development of hypertensive disease. The depression substudy, which enrolled 2,393 patients in the United States, will report quality-of-life (QOL) data, including information regarding energy and fatigue. The genotyping substudy will provide genomic DNA samples from approximately 15,000 patients in the United States, including Puerto Rico. Many candidate genes will be examined for polymorphisms that may predict outcomes and/or responses to various treatments.