OBJECTIVE: Recent research data suggest that inflammation and/or depression are associated with the development and progression of cardiovascular disease (CVD). Considering that depression may arise as a response to irrational beliefs according to the Ellis model of psychological disturbances and therapy, we sought to evaluate whether irrational beliefs are associated with plasma inflammatory factors in cardiovascular disease-free people. METHOD: From May 2001 to December 2002 we randomly enrolled 453 men (23-69 years old) and 400 women (24-71 years old) stratified by age and gender. C-reactive protein, interleukin-6, serum amyloid-A, tumor necrosis factor-alpha and white blood cells were measured in all participants. Detailed dietary characteristics of these people were assessed through a validated food frequency questionnaire. Subjects completed also the irrational beliefs inventory (IBI), which is a brief self-report measure consistent with the Ellis model of psychological disturbance and therapy and the Zung's Depression questionnaire. RESULTS: The IBI scores were similar in men and women (53+/-11 vs. 53+/-10, p = 0.83). IBI score was positively correlated with C-reactive protein (rho = 0.14, p = 0. 02), interleukin-6 (rho = 0.11, p = 0.02), tumor necrosis factor-alpha (rho = 0.21, p = 0.014) and white blood cell counts (rho = 0.14, p = 0.02). These associations were confirmed even after adjusting for age, sex, years of school, body mass index, physical activity status, depression level and food items consumed by the participants. CONCLUSION: These findings indicate that irrational beliefs are associated with increased inflammation process, among apparently healthy individuals.