Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.