The study, a subproject within a Hypertension Specialized Center of Research (SCOR), had five substudies between 1996 and 2001. The first classified hypertensives into relatively homogeneous subgroups according to intermediate phenotypes based on heritable biological traits, including anthropometric and neurohumoral data obtained by submitting selected subjects to a 3-day inpatient protocol, from which data were extrapolated and applied to stratify larger subject populations in order to enhance efficacy of subsequent genetic analysis. The second substudy genotyped subjects for chromosomal loci using approximately 350 highly polymorphic microsatellite markers spaced every 5-10 centimorgans (cM) along each chromosome. The strategy was to initially type markers in a select group of hypertensive kindreds that independently demonstrated linkage. The third substudy analyzed the genetic marker data for linkage using both parametric (lod score) and nonparametric (affected-pedigree-member) methods. Suggestive findings were pursued in the sib-pairs. The fourth substudy used the case-control method to confirm positive linkage from substudy 3 and to identify particular allele associations using methods of linkage disequilibrium and DNA pooling. The fifth substudy screened and assessed mutations in candidate genes linked to hypertension in patients and controls. A collaboration was established with the Framingham Heart Study, with linkage analyses conducted for hypertension in this cohort.