Background: The effect of cardiopulmonary bypass temperature and blood gas management on the brain is still controversial. This study was designed to compare the changes in S100beta protein concentration and Mini-Mental State Examination in patients undergoing cold (28degreesC) vs. warm (34degreesC) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). Methods: Sixty patients were randomly allocated to one of four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat, warm pH-stat). Serum S100beta concentrations were measured before CPB, directly after CPB, at 4.5 h and at 24 h after CPB. Mini-Mental State Examination was performed one day before surgery and on day five after the operation. Antegrade warm blood cardioplegia (37degreesC) was used in all patients, Results: There was no significant difference in postoperative S100beta protein levels between the four groups. Also, there was no interaction between bypass temperature and type of blood gas strategy on S100beta levels after bypass (directly after bypass, 4.5h and 24h after bypass). Mini-Mental State Examination score was not affected by blood gas strategy but it was significantly lower in patients undergoing cold cardiopulmonary bypass surgery: median (range), 26 (12-29) vs. 27 (23-30) in warm patients, P = 0.014. There was no significant correlation between Mini-Mental State Examination score 5 days after CPB and S100beta levels at any of the studied time-points after CPB. Conclusion: These results support the use of warm CPB (34degreesC) in patients undergoing coronary artery bypass surgery regardless of the type of blood gas strategy.