Serum paraoxonase circulates on a subfraction of high density lipoproteins and appears to use phospholipids on both low and high density lipoprotein particles as a physiological substrate. This functional relationship could explain the reported associations between common variation in the PON1 gene--at codons 55 and 192--and phenotypes related to atherosclerosis and lipoprotein metabolism. We evaluated associations between plasma lipoproteins and PON1 L/M55, PON1 Q/R192 and PON2 A/G148 polymorphisms in samples from two Canadian aboriginal populations, namely the Oji-Cree and the Inuit. In diabetic Oji-Cree, we found that carriers of PON1 M55 had a higher mean plasma triglyceride concentration than non-carriers. In non-diabetic Oji-Cree, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoporetein cholesterol and apo B than non-carriers. In Inuit, we found that carriers of PON1 M55 had higher mean plasma concentrations of total and low density lipoprotein cholesterol than non-carriers. The other polymorphic markers were not associated with variation in any plasma lipoprotein trait. Thus, the PON1 M55 allele appeared to be associated with deleterious changes in the plasma lipoprotein profile from two independent Canadian aboriginal samples. These results suggest that common variation in PON1 codon 55 is associated with variation of intermediate traits in plasma lipoprotein metabolism in aboriginal Canadians.