The endemic occurrence of favism in certain Mediterranean regions provided an investigative opportunity for testing in vivo the validity of claims as to the role of catalase in protecting human erythrocytes against peroxidative injury. Reduced activity of catalase was found in the erythrocytes of six boys who were deficient in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) and who were studied while suffering hemolysis after ingesting fava beans. Activity of catalase was further reduced when their red blood cells were incubated with aminotriazole. In contrast, minimal reduction of catalase activity was found, both with and without incubation with aminotriazole, in erythrocytes of a G6PD-deficient boy who had ingested fava beans 7 days earlier and in erythrocytes of seven G6PD-deficient men with a past history of favism. These results confirmed earlier studies in vitro indicating that catalase is a major disposer of hydrogen peroxide in human erythrocytes and, like the glutathione peroxidase/reductase pathway, is dependent on the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The effect of divicine on purified catalase and on the catalase of intact G6PD-deficient erythrocytes was similar to the previously demonstrated effect on catalase of a known system for generating hydrogen peroxide. This effect of divicine strengthens earlier arguments that divicine is the toxic peroxidative component of fava beans.