Since adducin modulates cellular sodium retention, its follows that ADD1, which encodes the alpha-subunit of adducin, is an attractive candidate gene for blood pressure variation. Association studies examining the relationship between polymorphism at ADD1 codon 460 (G460W) and both hypertension and blood pressure, which were performed in a variety of human population samples derived from different genetic backgrounds, have given inconsistent results. We examined the association between the ADD1 G460W polymorphism and variation in blood pressure in a sample of non-diabetic, largely normotensive Canadian Oji-Cree from an isolated community in Northern Ontario. Among 481 Oji-Cree subjects, we measured blood pressure and related clinical phenotypes and determined genotypes of ADD1 G460W. We observed an allele frequency of 0.08 for the ADD1 W460 variant, which is among the lowest so far observed in human populations. We found significant associations between variation in both systolic and diastolic blood pressure and gender, age, body mass index (BMI), and treatment for hypertension. However, we found no association between the ADD1 W460 allele and increased blood pressure, nor did we observe a higher frequency of the W460 allele in a hypertensive subgroup compared with normotensive subjects. While the low sample frequency of ADD1 W460 is consistent with the low sample prevalence of hypertension, the absence of a specific association with both blood pressure and hypertension suggests that the ADD1 W460 variant is not an important determinant of blood pressure among individuals of this genetic background.