Losartan binds selectively to the angiotensin II subtype 1 receptor, blocking the activity of angiotensin II. Losartan 50-100 mg/day was compared with atenolol 50-100 mg/day in patients with essential hypertension and left ventricular hypertrophy (LVH) [n = 9,193] in the randomized, double-blind Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Two substudies compared these drugs in patients with diabetes mellitus (n = 1,195) or isolated systolic hypertension (ISH) [n = 1326]. The target BP (<140/90 mm Hg) was achieved in approximate, equals 45% of losartan and atenolol recipients in the LIFE study. Significant regression of LVH occurred with losartan versus atenolol in the LIFE study, as well as in the diabetes mellitus and ISH substudies. In the LIFE study, although BP reduction was similar for the two treatments, the risk of a cardiovascular event (the composite of cardiovascular death, stroke, and myocardial infarction; primary endpoint), stroke, or new-onset diabetes mellitus was significantly lower with losartan than with atenolol. Losartan was generally well tolerated in patients with hypertension and LVH in the LIFE study. Significantly fewer losartan than atenolol recipients discontinued treatment because of adverse events, drug-related adverse events, or serious, drug-related adverse events.