Vasoconstrictor responses to prostaglandin F2 alpha and noradrenaline were investigated in ring segments of feline femoral, coronary and cerebral arteries incubated in calcium-free solutions containing different concentrations of magnesium (1.2, 4.4 and 13.2 mM). Contractions produced by prostaglandin F2 alpha and noradrenaline were depressed when calcium was omitted from the incubation solution. The presence of raised concentrations of magnesium (4.4 or 13.2 mM) in the tissue bath further depressed the prostaglandin F2 alpha and noradrenaline contractions in calcium-free medium. In a separate set of experiments the vessel wall contents of cAMP and cGMP were measured before and after the additions of 4.4 or 13.2 mM magnesium; stable relaxations by magnesium were noted but there was no parallel change in the vessel content of cAMP or cGMP. The results indicate that magnesium may interfere with the release of calcium from intracellular depots, and that neither adenylate cyclase, nor guanylate cyclase are involved in the dilator activity of magnesium in isolated arteries.