Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol, impeding atherosclerosis. The authors hypothesize that these medications may improve blood pressure by modifying the arginase-nitric oxide synthase system of erythrocytes. In this study, the effects of lisinopril alone versus lisinopril + simvastatin on erythrocyte and plasma arginase enzyme and nitric oxide metabolites are compared. Patients with atherosclerosis and hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher arginase activity is observed in erythrocytes from 100% of patients and mainly recovered after 12 and 24 weeks of treatment with lisinopril or lisinopril + simvastatin. Plasma arginase activity is 3 orders of magnitude lower than erythrocyte arginase activity in all participants, suggesting a lack of its clinical significance. Both treatments cause the increase in plasma $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ , $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ , and $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ in 100% of patients. Erythrocyte $$\hbox{ N }{\hbox{ O }}_{2}^{-}$$ + $$\hbox{ N }{\hbox{ O }}_{3}^{-}$$ concentration is greatly decreased in hypertensive patients but recovers after monotherapy and combined therapy. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit pronounced and equipotential normalizing effects on erythrocyte arginase and nitric oxide synthase activities.