Angiotensin-converting enzyme (ACE) inhibitors reduce systemic and coronary vasoconstriction by modulating sympathetic neuroeffector function and by decreasing sympathetic activation. Here, blood pressure, and tissue concentrations of noradrenaline and neuropeptide Y (NPY) were studied in normotensive and spontaneously hypertensive rats (SHR) after 2 weeks treatment with lisinopril (0.3 mg/day; osmotic mini-pump). MAP was reduced in both normotensive rats and SHR after lisinopril by 32 mm Hg and 66 mm Hg respectively (P < 0.001 compared to corresponding control rats). NPY levels were significantly higher in extracts of atria, kidney, spleen and adrenal of normotensive rats compared to SHR. Lisinopril treatment increased NPY levels in atria and skeletal muscle extracts of SHR by 15% and 70% respectively (P < 0.05). Lisinopril also significantly increased noradrenaline content of the atria by 16% in SHR (P < 0. 05). The decrease in MAP and increase in tissue levels of sympathetic neurotransmitters provide further evidence that inhibition of ACE decreases sympathetic neurotransmission leading to accumulation of stored neurotransmitters. Journal of Human Hypertension (2000) 14, 381-384