Disturbances in hormonal systems involved in sodium and water homeostasis are common during respiratory insufficiency. To investigate the role of hypercapnia, we designed a study to examine the hormonal response to acute hypercapnia induced at constant cardiac filling pressures and without hypoxemia. Seven sedated patients with COPD receiving mechanical ventilation were studied during five successive periods. Hemodynamics, arterial blood gases, and plasma hormone levels (atrial natriuretic peptide, renin, angiotensin II, aldosterone, vasopressin) were measured three times during 60 min of acute hypercapnia (52 +/- 5 mm Hg) and at control periods, before (36 +/- 4 mm Hg) and after (42 +/- 3 mm Hg) acute hypercapnia. During acute hypercapnia, mean pulmonary arterial pressure and cardiac output were increased without variation of other measured cardiorespiratory data and hormonal levels when compared with control values. After acute hypercapnia, cardiorespiratory variables returned to control values without variations of hormonal levels. Our results show that moderate acute hypercapnia does not significantly influence the hormonal levels when cardiac filling pressures and sympathetic tone remain stable. We suggest that changes in those plasma hormones involved in salt and water homeostasis during acute hypercapnia are secondary to hemodynamic changes induced by acute respiratory failure and not to acute hypercapnia per se.