Although there is a brain renin-angiotensin system, its mechanisms of control are not fully understood. We studied the effect of oral administration of the AT(1) receptor antagonist losartan on brain aminopeptidase (AP) activity, which plays a major role in neuropeptide metabolism. Six AP activities, related and non-related with the angiotensin (Ang) metabolism, were measured in their soluble and membrane-bound forms in the frontal cortex of control animals and rats treated with losartan, chronically administered via the drinking water. The results demonstrate that soluble pGluAP and membrane-bound AspAP and GluAP increased significantly in losartan-treated animals, indicating that the blockade of the AT(1) receptor stimulates the activity of AP involved in the Ang metabolism. Moreover, the blockade of the AT(1) receptor induces changes not only in the brain angiotensin metabolism, but probably also in that of other neuropeptides.