In Milan hypertensive rats, a variant in the alpha-adducin gene has been shown to account for approximately 50% of the interindividual variation in blood pressure levels between these animals and their normotensive counterparts. Additional studies have suggested that a polymorphism within exon 10 of the human alpha-adducin gene (Gly-460-Trp) may be associated with hypertension and salt sensitivity. On the basis of these observations, we investigated variation within or near the human alpha-adducin gene for linkage and association with a locus influencing blood pressure levels in 281 nuclear families (774 siblings aged 5 to 37 years; 380 parents aged 26 to 57 years), selected from the white population of Rochester, Minnesota, without regard to health. Sib pair linkage analyses (n = 852 sibling pairs) using a dinucleotide repeat marker (D4S43) that maps approximately 660 kb from the alpha-adducin gene provided no evidence of linkage between this marker locus and a locus influencing systolic, diastolic, or mean blood pressure levels. Allele frequencies for the Gly-460-Trp polymorphism were similar to those reported in other white populations (Gly = 0.812, Trp = 0.188); however, this polymorphism was not associated with any measure of blood pressure level in either parents or siblings. Therefore, variation within the alpha-adducin gene does not appear to have a major influence on measures of blood pressure in white families from Rochester, Minnesota.