BACKGROUND Chronic angiotensin converting enzyme (ACE) inhibitor therapy with enalapril, captopril or ceranopril prevents the development of cerebrovascular lesions in stroke-prone spontaneously hypertensive rats (SHRSP) given a 1% NaCl solution to drink, with little or no effect on systolic blood pressure. OBJECTIVE To determine the effect of the orally active angiotensin (Ang) II receptor antagonist losartan on blood pressure and stroke in SHRSP. METHODS Losartan or vehicle was chronically administered to saline-drinking SHRSP, and systolic blood pressure was monitored. The effect of losartan on arterial blood pressure measured by radiotelemetry in enalapril-treated SHRSP was also examined. RESULTS Oral losartan at 30 mg/kg per day delayed the development of severe hypertension and prevented stroke in saline-drinking SHRSP. Losartan therapy at a dose of 10 mg/kg per day did not affect the systolic blood pressure elevation but prevented the occurrence of cerebrovascular lesions at least until 28 weeks of age. Radiotelemetric monitoring of arterial blood pressure in enalapril-treated, saline-drinking SHRSP over a 3-month period verified the maintenance of severe hypertension without any strokes. Treatment with oral losartan at a dose of 30 mg/kg did not affect the blood pressure of SHRSP chronically treated with enalapril. CONCLUSIONS These results are consistent with the theory that Ang II has an effect on the pathophysiology of cerebrovascular lesion development in saline-drinking SHRSP. These findings indicate that losartan has a protective action, similar to that previously observed with ACE inhibitors, against the development of cerebrovascular lesions in SHRSP in the absence of a blood pressure fall.