To determine the effects of copper deficiency on the vascular wall, female rats of the Wistar King A strain were fed a copper-deficient diet (0.58 ppm), and all delivered pups were kept on the same diet. The copper level of sera of all copper-deficient animals was significantly lower (10.6 fig/ dl) than that of the controls (141.4 jug/dl). The body weight of copper-deficient rats was about 40% of the controls at 12 weeks of age. Copper deficiency produced a reduction in norepinephrine (NE) content in aortic tissue (40%), but not in portal veins. There was an increase in sensitivity of aortic tissue to NE. Depolarization of the muscle membrane of pulmonary arteries in response to NE decreased at high NE concentrations. The tensile strength of the aortas decreased, and there was an increase in the active contraction and a shift of the maximum amplitude to the right in the aortic length-tension curve. A reduction in aortic elastin and collagen contents was observed on electron micrographs. There also was a prolongation of relaxation times after contraction produced by NE, in a manner similar to that observed after 6-hydroxydopamine (6-OHDA) treatment. Also, in aortas, copper deficiency produced a resistance to NE depletion by chemical sympathectomy (6-OHDA), whereas in portal veins, there was no reduction in NE content after treatment with 6-OHDA (50 mg/kg, ip). These results suggest that rupture of copper-deficient aortas is due mainly to a decrease in elasticity of the aortic wall, probably as a result of reduction in elastin and collagen. The changes observed in the membrane and contractile properties of elastic arterial smooth muscle cells under conditions of copper deficiency probably are compensatory mechanisms which serve to protect the vascular wall.Circ Res 46: 681-689, 1980