High-sensitivity C-reactive protein (hs-CRP) is a biomarker that correlates with atherothrombotic risk and outcome. hs-CRP is influenced by various modifiable and non-modifiable factors. We studied the relationship between ethnic background and hs-CRP level, among the Jewish population in Israel. A total of 3659 men and 2180 women were divided into two ethnic groups (Ashkenazi and Sephardic Jews), based on the knowledge of Jewish immigration patterns throughout the centuries. Mean hs-CRP levels were calculated for each group and were adjusted for various factors known to influence hs-CRP. Sephardic Jews were found to have higher adjusted mean hs-CRP levels (2.0 mg l(-1) for men and 3.9 mg l(-1) for women) compared with Ashkenazi Jews (1.5 mg l(-1) for men and 2.9 mg l(-1) for women). Ethnic background emerged as an independent significant predictor of hs-CRP levels. We demonstrated that ethnicity is an important factor when considering hs-CRP as a marker of atherothrombotic risk.