Geneticists seek to understand the interaction between genetic and environmental causes of phenotypic variation among individuals in a population. Clinical studies have established that an individual's blood pressure (BP) level is the consequence of the interaction of biologically determined characteristics of the nervous, renal, endocrine and circulatory systems with factors that define one's environment, such as dietary salt, stress and exercise. The many genes that orchestrate the development of these biologically determined characteristics are expected to determine one's BP level, one's increase in BP with age and one's BP response to changes in the environment. One consequence of such a multifactorial etiology is that there are multiple combinations of genetic and environmental factors that may lead to the same BP level. The prevention and control of hypertension will be enhanced when intervention strategies take into account this etiological heterogeneity in determining the hypertensive endpoint. We are pursuing a level crossing strategy in the study of the causes of interindividual BP differences. According to this approach relevant phenotypes that link genetic and environmental factors with blood pressure levels are identified, the genetic contribution to variability in these phenotypes is estimated and then the contribution of this genetic etiology to blood pressure variability is evaluated. We have successfully carried out such a level crossing approach in our investigations of the genetics of red cell sodium lithium countertransport and the relationship between sodium lithium countertransport and blood pressure. A single gene effect on red cell sodium lithium countertransport levels is the only single gene known to affect interindividual blood pressure variability.