Myeloperoxidase, a heme enzyme secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins. This study demonstrates that myeloperoxidase is present in human atherosclerotic lesions. Western blotting and immunostaining revealed that myeloperoxidase is expressed in atherosclerotic tissue, with immunoreactive protein and authentic myeloperoxidase binding to a lectin column and eluting with methyl mannoside. Peroxidase activity in detergent extracts of atherosclerotic lesions bound to a lectin column and generated hypochlorous acid (HOCl), indicating enzymatically active myeloperoxidase. Immunostaining showed that myeloperoxidase is present in macrophage-rich regions of transitional lesions and adjacent to cholesterol clefts in advanced atherosclerotic lesions. These findings suggest that myeloperoxidase contributes to atherogenesis by catalyzing oxidative reactions in the vascular wall. Myeloperoxidase generates reactive species that damage lipids and proteins, potentially promoting atherosclerosis. The enzyme is expressed in human vascular lesions and may play a pivotal role in the development of atherosclerotic lesions.Myeloperoxidase, a heme enzyme secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins. This study demonstrates that myeloperoxidase is present in human atherosclerotic lesions. Western blotting and immunostaining revealed that myeloperoxidase is expressed in atherosclerotic tissue, with immunoreactive protein and authentic myeloperoxidase binding to a lectin column and eluting with methyl mannoside. Peroxidase activity in detergent extracts of atherosclerotic lesions bound to a lectin column and generated hypochlorous acid (HOCl), indicating enzymatically active myeloperoxidase. Immunostaining showed that myeloperoxidase is present in macrophage-rich regions of transitional lesions and adjacent to cholesterol clefts in advanced atherosclerotic lesions. These findings suggest that myeloperoxidase contributes to atherogenesis by catalyzing oxidative reactions in the vascular wall. Myeloperoxidase generates reactive species that damage lipids and proteins, potentially promoting atherosclerosis. The enzyme is expressed in human vascular lesions and may play a pivotal role in the development of atherosclerotic lesions.