We investigated effects of the first orally active atriopeptidase inhibitor UK 79300 (Pfizer Clinical Research, UK) on left ventricular hydraulic load in patients with congestive heart failure NYHA II and III. In our study, 6 patients received 200 mg and 4 patients received 400 mg of UK 79300, and 4 patients received placebo (controls). Before and 90 min after oral administration of UK 79300 or placebo aortic input impedance was assessed to characterize left ventricular hydraulic load. Plasma levels of atrial natriuretic peptide (ANP) significantly increased by 126% after 200 mg and by 141% after 400 mg of UK 79300, but remained unchanged in control patients. Mean arterial pressure and flow, resistive term, characteristic impedance and oscillatory aortic input pressure power showed minor changes without statistical significance on an intergroup comparison. We conclude that acute atriopeptidase inhibition by UK 79300 effectively increases endogenous ANP levels up to 2.5-fold. However, these changes were not accompanied by significant effects on left ventricular hydraulic load.