The cellular and intracellular metabolization sites of the tissue hormone and paracrine compound histamine as a source for the indirect and potentially toxic or physiological mediator molecule H2O2 are not yet known. Therefore, in the present study, histamine was used as the substrate in a cerium-diaminobenzidine-H2O2-Co procedure to visualize for the first time the oxidative deamination and H2O2-production sites of this amine in various laboratory animals. Diamine oxidase (DAOX) was shown to be the responsible enzyme. With the exception of marmosets, all species could deaminate histamine oxidatively and form H2O2. In most species, H2O2 was produced by DAOX from histamine in small intestinal enterocytes; in rats H2O2 was generated in all vascular and non-vascular smooth muscle cells; in guinea-pigs only smooth muscle cells in the digestive tract and uterus and in addition the cardiac and gastric capillary endothelium and hepatic sinusoidal endothelium produced H2O2. Furthermore, in some species H2O2 was generated by DAOX with histamine as the substrate in certain renal, adrenal and splenic cell types. While H2O2-production in enterocytes may derive from luminal-borne histamine, i.e., from histamine of foreign origin, the formation of H2O2 in the other cells suggests endogenous (mast cell, basophilborne) histamine as the substrate and H2O2 source.