OBJECTIVE Cytokine response after cardiac surgery may be genetically influenced. A study was carried out to investigate the relation between cytokine gene expression in peripheral blood mononuclear cells, genotype, and clinical events after cardiac surgery. METHODS A case-control study was performed. METHODS Cardiac intensive care unit in a university hospital. METHODS A total of 82 patients having elective cardiac surgery were divided into those having uncomplicated recovery (n = 48) or recovery complicated by hyperlactatemia or requirement for inotropic support (n = 34). METHODS The relative change in peripheral blood mononuclear cell tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) messenger RNA 1 and 6 hrs after cardiopulmonary bypass was compared with a baseline preoperative level using quantitative reverse transcriptase polymerase chain reaction. DNA was analyzed for carriage of TNF-alpha and IL-10 polymorphic alleles. RESULTS Cardiopulmonary bypass was longer in duration in the complicated group. TNF-alpha gene expression decreased and IL-10 gene expression increased in peripheral blood mononuclear cells after surgery when compared with preoperative levels. One hour after cardiopulmonary bypass, the complicated group had more TNF-alpha and less IL-10 messenger RNA production than the uncomplicated group. The IL-10/TNF-alpha ratio was greater in uncomplicated than in complicated recovery patients. An IL-10 haplotype was identified that was less frequent in the complicated group. There was no difference between groups in TNF-alpha genotype. On multivariate analysis, cardiopulmonary bypass time and the IL-10/TNF-alpha messenger RNA ratio were independent predictors of outcome. CONCLUSIONS There is a predominant anti-inflammatory cytokine response after uneventful cardiac surgery. IL-10 may have a protective role after cardiac surgery.