In this article we will examine the potential impact of molecular biology on hypertension research. We will review the available molecular techniques, which include gene cloning, transient and stable expressions, as well as the use of transgenic animals. To facilitate our discussion, we will focus primarily on research of the renin gene. Renin provides a useful model that illustrates the power of biotechnology in providing detailed structural and biochemical information on a complex protein that exists in low quantities in vivo. Studies of its messenger RNA and gene expression have resulted in an improved understanding of the biology of the renin system and in generating new hypotheses. These approaches can be generalized to studies of other vasoactive hormones, contractile protein, and other gene products related to cardiovascular regulation. To elucidate the role of a specific gene in genetic hypertension, we will discuss the use of genetic markers in cosegregation or linkage analysis. Finally, we will examine the potential of transgenic animals in the study of regulation of gene expression in the whole animal and the contribution of selective genes to hypertension. We believe that molecular biology complements the biochemical and physiological approaches and provides new opportunities for furthering our concept of hypertension mechanisms. (Hypertension 1989;13:731-740) B lood pressure is regulated by multiple control mechanisms. Abnormalities in the regulation of one or several of these control systems may result in a transient or a sustained elevation in blood pressure. For instance, renal, endocrine, neurogenic, cardiogenic, and vascular mechanisms have each been demonstrated to participate in the development of experimental hypertension as well as in the pathogenesis of secondary forms of human hypertension. However, the etiology and pathogenetic mechanisms of essential hypertension are still enigmatic. Although many altered physiological responses and biochemical parameters have been reported, both in patients with essential hypertension and in animal models of genetic hypertension, it remains unclear which of the various reported changes are primary (i.e., causative) and which are secondary (i.e., the result of hypertension). Physiological and biochemical events are usually modulated by multiple related