The aim of this study was to investigate the relationships between angiotensin-converting enzyme (ACE) activity in serum and skeletal muscle to blood pressure and the long-term antihypertensive effects of fosinopril and atenolol. We examined 50 hypertensive patients randomized to receive 20 mg fosinopril or 50 mg atenolol daily for 16 weeks. ACE activity was measured in biopsy specimens from skeletal muscle. Measurements of office and ambulatory blood pressure, serum ACE, and left ventricular wall thickness were also performed. The same investigations were performed in a cross-sectional study of 50 healthy elderly men. Muscle ACE correlated inversely to blood pressure in cross-sectional analyses in both populations (p < 0.05). During atenolol treatment muscle ACE activity tended to increase (14%, p = 0.059), and this increase correlated inversely to the changes in standing systolic and diastolic blood pressure (r = -0.62, p = 0.0044, and r = 0.54, p = 0.016, respectively). Muscle ACE was also inversely correlated to left ventricular wall thickness when the two populations were pooled (r =-0.29, p = 0.0053). In the fosinopril group, muscle ACE activity was not different during treatment than at baseline (-2. 1%, p = 0.68). The inverse relationship between blood pressure and muscle ACE levels in this study indicate that muscle tissue ACE levels are influenced by haemodynamic factors in humans.