Abstract. The effects of angiotensin‐converting‐enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y‐like immunoreactivity (NPY‐LI), substance P (SP‐LI), calcitonin gene‐related peptide (CGRP‐LI), vasopressin (ADH‐LI), atrial natriuretic peptide (ANP‐LI) and renin activity (PRA) in patients with severe CHF (NYHA III‐IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I‐II). Catecholamines and NPY‐LI were increased to the same extent in both groups with severe CHF. CGRP‐LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP‐LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP‐LI level of 4.05±0.79 pmol l^−1^, compared to a concentration of 2.28±0.30 pmol l^−1^ (P < 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP‐LI and the serum sodium levels (r = —0.68, P < 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH‐LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP‐ LI level was increased to a similar extent in both groups.