Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) and lipoprotein(a) [Lp(a)] have been implicated as cardiovascular disease risk factors, and are differentially regulated across ethnicity. We investigated the association between Lp-PLA 2 activity and allele-specific apolipoprotein(a) [apo(a)] levels in a bi-ethnic population.Lp-PLA 2 activity, Lp(a) and allele-specific apo(a) levels were determined in 224 African Americans and 336 Caucasians.Lp-PLA 2 activity level was higher among Caucasians compared to African Americans (173±41nmol/min/ml vs. 141±39nmol/min/ml, P<0.001), and positively associated with Lp(a), total and LDL cholesterol, triglyceride, apolipoprotein B-100, and negatively with HDL cholesterol levels in both ethnic groups. The association between Lp-PLA 2 activity and Lp(a) was stronger among African Americans compared to Caucasians (R=0.238, β 1 =3.48, vs. R=0.111, β 1 =1.93, respectively). The Lp-PLA 2 activity level was significantly associated with allele-specific apo(a) levels for smaller (<26 K4 repeats) apo(a) sizes in both ethnic groups (P=0.015 for African Americans, P=0.038 for Caucasians). In contrast, for larger (>26 K4 repeats) apo(a) sizes, high Lp-PLA 2 activity levels were associated with higher allele-specific apo(a) levels in African Americans (P=0.009), but not in Caucasians.The association between Lp-PLA 2 activity and allele-specific apo(a) levels differs across African American-Caucasian ethnicity.