The gasotransmitter nitric oxide was classified as the first endothelium-derived relaxant factor, and opened a new era in cardiovascular research. Another small gas, sulfur dioxide (SO2), can also be generated endogenously in mammals. Recent studies have shown that SO2 may play important roles in the cardiovascular system. At low concentrations, the vasodilatory effect of SO2 is endothelium-dependent. The vasodilation induced by an endothelium-derived relaxant factor is achieved by the opening of potassium channels, and hyperpolarization of the membranes of vascular smooth muscle cells. This feature is in accordance with that of SO2. The vasodilatory effect of SO2 is related to the opening of adenosine triphosphate-sensitive potassium channels and high-conductance calcium-activated potassium channels. The 3'-5'-cyclic guanosine monophosphate pathway and activation of nitric oxide synthase are also involved in the endothelium-derived relaxant factor effect of SO2. The vasodilatory effect of gaseous SO2 is much stronger than that of its derivatives (bisulfite and sulfite). It is suggested that SO2 may be a candidate endothelium-derived relaxant factor, which could lead to a new era of research into cardiovascular disease in mammals.