Endogenous peroxidatic activity has been demonstrated at the ultrastructural level in large arteries of rabbit and rat using diaminobenzidine. The reaction was positive in endothelial cells of both species and also in the smooth muscle cells of rat arteries. The reaction product was localized in the nuclear envelope and endoplasmic reticulum of the reactive cells. Since the enzymatic activity was extremely sensitive to fixation, best visualization was obtained in unfixed, directly incubated tissues in which additional mitochondrial staining occurred due to the activity of endogenous cytochrome c/cytochrome oxidase system. The peroxidatic activity was partially sensitive to cyanide and could be completely abolished by azide and aminotriazole. It has been suggested that the observed endogenous peroxidatic activity of the arterial wall components reflects the activity of prostaglandin endoperoxide synthetase and, indirectly, production of prostacyclin (PGI2).