Hypertension affects approximately 20 to 30% of individuals in industrialized countries, and is commonly believed to develop on the basis of both genetic and environmental factors. The identification of genes susceptible to the most frequent form of hypertension, commonly referred to as "essential" hypertension, is hampered by the fact that blood pressure is a poorly defined phenotype that is modulated by multiple factors, such as gender, race, body mass etc., and that the definition of hypertension depends on a rather arbitrarily chosen cut-off value. Hence, more progress has been made in the identification of genes responsible for rare autosomal dominant forms of hypertension, such as Liddle's disease. This review focuses on an experimental approach that attempts to define candidate genes for essential hypertension using immortalized cells from well characterized normotensive and hypertensive subjects. From the presently available results, one attractive speculation is that an increased intracellular signal transduction caused by an enhanced reactivity of Gj-type G proteins represents a genetically fixed trait that renders affected individuals susceptible to essential hypertension.