BACKGROUND: It is known that proinflammatory and anti-inflammatory cytokines are released during and after cardiopulmonary bypass (CPB) in infants and children. Sex steroids are known to have immunomodulatory functions, and release of the anti-inflammatory cytokine IL-10 is stimulated by progesterone in vitro. The purpose of the present study was to investigate the plasma levels of progesterone, IL-8 (proinflammatory cytokine) and IL-10, and to relate them to sex and postoperative morbidity. METHOD: Eighteen infants and children (eight female) undergoing CPB were prospectively studied. Plasma levels of progesterone, IL-8 and IL-10 were determined before and 10 min after the start of CPB, and immediately after CPB; and 6 h, 24 h, 3 days and 7 days postoperatively. Organ dysfunction was identified on the basis of arbitrarily defined criteria. RESULTS: After CPB, all patients showed significant increases in plasma levels of progesterone, IL-8 and IL-10. Plasma levels of IL-10 were significantly higher in female patients, except for during the immediate postoperative period. According to the criteria used, six out of 10 male patients, but none of the female patients developed multiple organ dysfunction (MOD). CONCLUSION: The present study shows that CPB induces a significant and marked increase in plasma levels of progesterone in infants and children. Studies of administration of progesterone-blocking substances to male and female animals may help to elucidate the roles of sex and progesterone in the setting of CBP.