Paraoxonase (PON1) is tightly associated with high-density lipoprotein particles and is believed to contribute to the prevention of atherosclerosis by metabolizing oxidized lipids. PON1 also hydrolyses the bioactive oxon forms of organophosphorus pesticides such as parathion, diazinon and chlorpyrifos. Two common polymorphisms have been identified in the coding sequence of human PON1: L55M and R192Q. Several previous studies have found that the presence of thePON1R192allele raises the risk of cardiovascular disease while others found no correlation. The studies, however, have focused on the genotype of PON1 and not the expression level of the protein. We found that the PON1 expression level in plasma, as determined by the rates of paraoxon and diazoxon hydrolysis, varies widely among individuals and within a genotype. Previous studies found that individuals having Met at PON155have lower levels of both PON1 mRNA and activity. In this study, we determined the plasma activity levels of PON1 and examined the relationships betweenPON155genotype and PON1 level. As withPON1192, we found considerable overlap in activity among thePON155genotypes. Of the 317 individuals whose PON1 status was determined in this study, 48.9% werePON1Q192homozygotes. Analysis of the PON1QQ192population showed that while the average PON1 activity (diazoxon hydrolysis) was 12266 U/L for PON1LL55and 7777 U/L for PON1MM55, a given PON1MM55individual could have more than twice the activity of a PON1LL55individual. PON1 status, which includes PON1 level as well asPON1192genotype, may be a better predictor for cardiovascular disease or organophosphate susceptibility thanPON1genotype alone.