In the rat, the results of genetic linkage studies by "candidate" gene or "positional mapping" approaches have suggested that DNA sequences that regulate blood pressure may be located in the vicinity of the kallikrein gene family on chromosome 1, the gene for angiotensin-converting enzyme on chromosome 10, the renin gene on chromosome 13, and the major histocompatibility complex on chromosome 20. Some studies have also suggested that blood pressure regulatory genes may be located on the sex chromosomes. Pending the results of confirmatory studies, these experiments should be interpreted with caution. However, with confirmation of these studies, it should be possible to create a variety of new animal models that will provide excellent opportunities for investigating the molecular, biochemical, and physiologic determinants of high blood pressure. In addition, in genetic studies in humans with essential hypertension, it may be worthwhile to target chromosome regions that are homologous to those implicated in linkage studies of hypertension in rodents. By narrowing the focus on selected areas of the genome, experimental linkage studies in the rat may also be used to guide the detailed molecular approaches ultimately required to identify the specific DNA sequence alterations that give rise to increased blood pressure.