Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. The aims of this study were to identify the factors affecting MPO serum concentration, to study the familial resemblance of MPO levels and to investigate the association between newly described MPO polymorphisms as well as the G-463A one and MPO levels in a healthy population. MPO serum concentrations were measured by an enzymatic immuno-assay (EIA) in 82 healthy families of the STANISLAS Cohort and MPO genotype, determination was performed using PCR-restriction fragment length polymorphism or allele specific oligonucleotide assay. MPO concentrations were significantly higher in parents than in offspring. The factors affecting MPO levels were age, the number of white cells, smoking in fathers and oral contraceptive intake in mothers. They explain from 12.4% up to 35.9% of MPO variability in men and women, respectively. Family correlations of MPO concentrations were of similar magnitude. The -129A allele of a newly described G-129A substitution was significantly associated with decreased MPO levels, whereas the -463A allele was suggested to be associated with increased levels of lipid variables. In this study, we identified factors affecting MPO serum concentrations and showed that molecular variations of the gene have only a weak influence on MPO variability. In contrast, the association between the G-463A polymorphism and lipid levels would suggest a possible implication of MPO in the risk of cardiovascular diseases. These results have to be confirmed and further investigations will be conducted in that way.