To examine the interrelations between humoral systems involved in the circulatory and body fluid volume homeostasis of patients with chronic obstructive pulmonary disease (COPD), we measured plasma levels of renin activity (PRA), aldosterone (Aldo), and atrial natriuretic factor (ANF) in 14 patients with stable COPD who used continuous O2 therapy. Hemodynamics, blood gases, and plasma hormone levels were measured (1) while patients received supplemental O2; (2) after 30 min O2 discontinuation; and (3) after a 30-min period of 96% O2 breathing. Plasma immunoreactive ANF concentrations were 196 +/- 50 pg/ml during O2 breathing and were positively related to transmural pulmonary arterial wedge pressure (tPpaw, r = 0.90, p less than 0.001) and to PaCO2 (r = 0.57, p less than 0.02). Compared to normal subjects matched for age and sex, patients had higher plasma ANF levels (196 +/- 52 versus 72 +/- 6 pg/ml, p less than 0.01), similar PRA (2.1 +/- 0.5 versus 1.3 +/- 0.3 ng/ml/h, NS), and slightly lower plasma Aldo (98 +/- 17 versus 156 +/- 19 pg/ml, p less than 0.05). Discontinuation of O2 while decreasing PaO2 from 70 +/- 3 to 50 +/- 3 mm Hg resulted in a significant increase in pulmonary arterial pressure (Ppa) from 29 +/- 2 to 32.5 +/- 3 mm Hg (p less than 0.01) and cardiac index (Cl) from 3.6 +/- 0.1 to 3.9 +/- 0.1 L/min/m2 (p less than 0.01) and a decrease in systemic arterial pressure (Psa) from 96 +/- 3 to 91 +/- 2 mm Hg (p less than 0.05); transmural cardiac filling pressures and pulmonary vascular resistance (PVR) were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)