The study was undertaken to determine whether polymorphic variants of the alpha-adducin gene are associated with isolated systolic hypertension (ISH) in elderly Australian Caucasians. Participants were classified with ISH (n = 87, systolic blood pressure (SBP) > or =160 mm Hg and diastolic blood pressure (DBP) < or =90 mm Hg) or normotension (n = 124, SBP <140 mm Hg and DBP <90 mm Hg with no family history of hypertension). To collect demographic data, a structured questionnaire was used. DNA was extracted using standard techniques from 211 subjects (age range 61-89, mean age 73 +/- 6.6 years, male: female ratio 1.1:1). Genotypes (gly/gly, trp/gly and trp/trp) were assigned in triplicate by polymerase chain reaction (PCR) followed by electrophoresis, using a laser scanning electrophoresis unit. The validity of the method was confirmed by sequencing. Frequencies of allele distribution in ISH or control groups were determined by Chi-square tests and a stepwise logistic regression model, which controlled for potential confounders, was used to examine any independent association between alpha-adducin genotypes or alleles with ISH and normotensive controls. Mean BP (+/- s.d.) was: 170/79.8 +/- 14.9/8.3 mm Hg and 122.1/ 73.4 +/- 8. 8/7.6 mm Hg in the ISH and normotension groups respectively. The unadjusted allele and genotypes frequencies were not significantly different in the ISH patients groups compared with normotensive controls (chi2 = 1.59, P = 0.45 and chi2 = 1.23, P = 0.28 respectively). In this elderly cohort, after adjustment for potential confounders, no statistically significant association was found between alpha-adducin genotype and SBP (P = 0.65 for homozygotes, P = 0.59, for heterozygotes), DBP (P = 0.49 homozygotes, for heterozygotes P = 0.45) pulse pressure (P = 0.87 homozygotes, for heterozygotes P = 0.95) diagnosis of ISH (P = 0.72 for homozygotes, P = 0.68 for heterozygotes). However age and renal disease predicted the diagnosis of ISH (P = 0.001, P = 0.459, respectively), a large pulse pressure (P < 0.0001, P = 0.033, respectively) and a higher SBP (P < 0.0001, P = 0.025, respectively) in this large cohort of elderly Australian Caucasian volunteers. Journal of Human Hypertension (2000) 14, 199-203.