Two patients with Wilson disease who presented with severe hemolytic anemia are described. One was noted to have unusually high serum copper levels (369 micrograms/100 ml). A review of similar such patients in the literature suggests that, rather than having a low serum copper, patients with hemolysis accompanying Wilson disease have very high serum copper levels. For this reason, in vitro studies of the toxic effects of copper on erythrocytes were undertaken. It was found that, although copper does not have a major direct inhibitory effect on glycolytic enzymes such as hexokinase, the metal does inhibit hexokinase as a consequence of its interaction with oxyhemoglobin. However, such inhibition does not appear to be a major factor in copper-induced hemolysis. On the other hand, the addition of the lipid antioxidant butylated hydroxyanisole (BHA) suppresses hemolysis in copper-treated cells. These experiments suggest that the primary toxic effect of copper is mediated through its oxidant actions on membrane phospholipids rather than through its potential inhibitory effects on intracellular enzymes.