Two new automated, highly sensitive methods for the measurement of C-reactive protein (CRP) were compared using blood samples from active and retired health care workers (116 males, 114 females). The regression equation was y=1.115x-0.0267 forthe Kamiya K assay immunoturbidimetric method (x) vs. the Behring BNII nephelometric method (y) with medians (IQR) of 0.156 (0.081 to 0.276) and 0.150 (0.060 to 0.240) mg/dl, respectively. Significant differences in hsCRP values between males and females were observed (p=0.013 and p=0.0018 for Behring and Kamiya methods, respectively). This gender difference in CRP levels was confirmed by analysis of serum samples from 1,114 individuals (639 males and 475 females) obtained through Mayo Medical Laboratories reference services, which represents participants from across the United States. The gender difference, which was confirmed (p<0.0001), was independent of age differences as assessed by multiple regression analysis. The observed gender differences have important implications for the establishment of cut-off points for cardiovascular risk stratification.