Data are reviewed which suggest that the peripheral vasodilatation and hypotension which result from ingestion (or administration) of ethanol may, in large part, be a consequence of its direct actions on vascular smooth muscle cells, both at the macro- and microcirculatory levels. At least two mechanisms appear to contribute to this vasodilator effect: (1) inhibition of the normal rhythm or vasomotion (spontaneous mechanical activity) of vascular smooth muscle; and (2) depression of the contractile responses to endogenous neurohumoral substances that play a role in maintaining vascular tone and regulation of blood flow. In addition, data is presented to indicate that human umbilical blood vessels are extremely sensitive to the vasospasmic actions of ethanol. The data acquired so far suggest that the dilator actions are related causally to interference with movement and/or translocation of Ca2+ across the vascular membranes. In addition, these actions appear to resemble the peripheral vascular effects of general anesthetics. Evidence is also reviewed which indicates that certain concentrations of ethanol, acting on specific peripheral blood vessels (e.g., cerebral arteries), can induce direct contractile responses (dose-dependent), and potentiate certain hormones, the effects of which are dependent upon free, ionized Ca2+ ions. None of these actions nor the vasodilator actions can be attenuated, prevented or mimicked by any known pharmacologic antagonist. Lastly, this chapter cites recent findings, in experimental animals, maintained on liquid diets of ethanol, which may provide insights into why a high incidence of hypertensive vascular disease has been noted in alcoholics.