This supplement to the Journal of Cardiovascular Pharmacology reports on the proceedings of a symposium entitled 'Endothelins in Cardiovascular Disease' that was held in Padua on 12-13 June, 1998 as a satellite symposium of the 17th Scientific Meeting of the International Society of Hypertension. Compelling experimental and clinical evidence has indicated that the endothelium plays a pivotal role in the autocrine-paracrine control of vascular tone as well as in the regulation of vascular structure. Under normal conditions a balance between endothelium-derived relaxing factors (EDRFs) and endothelium-derived constricting factors (EDCFs) results in the maintenance of a normal vascular resistance and structure. Under pathological conditions the endothelium synthesizes EDCFs in excess of EDRFs. The most important EDCF endothelin-1 (ET-1), is produced from the cleavage of the precursor big ET-1 by a specific endothelin-converting enzyme (ECE). So far three ECEs, termed ECE-1, ECE-2 and ECE-3, have been identified. However in humans the most important seems to be ECE-1 of which three isoforms, termed A, B, and C, as a result of alternative mRNA splicing, exist. Endothelin-1 acts on two specific receptors termed ETA, located in vascular smooth muscle cells (VSMC) and ETB located in both endothelial cells and in VSMC. Activation of ETA receptor results in very potent and long-lasting vasoconstriction and mitogenesis, while activation of ETB receptors produces different physiological responses in different cell types. In endothelial cells the ETB receptor mediates the release of EDRFs, mainly nitric oxide and adrenomedullin, whereas the ETB in VSMC mediates vasoconstriction. The preproendothelin-1 gene is subjected to complex regulation by several biochemical and biophysical signals. Recent evidence indicates that a number of cardiovascular risk factors, such as oxidized low-density lipoprotein, diabetes, hypoxia, aging and hypertension are associated with enhanced ET-1 biosynthesis. Thus, overexpression of ET-1 in the setting of reduced nitric oxide availability could represent an important detrimental factor in several pathological conditions characterized by excess vasoconstriction and vascular remodeling, such as hypertension, congestive heart failure, pulmonary hypertension and renal damage. Since the discovery of ET-1 by the group of investigators led by Professor Masaki in 1988 an ever-increasing number of papers, currently exceeding 4500, have appeared. The Journal of Cardiovascular Pharmacology has already published the proceedings of several international symposia on ET-1 and therefore it is almost a tradition for the most relevant collections of contributions on this topic to appear in this journal. In this supplement we have asked all contributors, who are internationally renowned authorities in the field of ET-1 research, to provide updated information on selected topics, ranging from molecular biology and pharmacology to clinical aspects, in the form of mini-reviews. Since effective endothelin receptor antagonists and ECE-1 inhibitors have become available a number of interesting data have been generated, particularly with regard to the treatment of congestive heart failure and hypertension. This is why we are confident that this supplement will satisfy the interest of the readers.