Histamine has been found biochemically in the mammalian vascular wall. This study was undertaken in an effort to identify the presence of specific histamine-containing cells in walls of large blood vessels such as femoral artery and vein, brachial artery and vein, mesenteric artery and vein, renal artery and vein, and aorta. Segments of vessels from rats, cats, dogs, sheep, cows, humans and chickens were examined. Sections were prepared from fresh tissue by vibratome, from frozen tissue by cryostat and from freeze-dried and fixed tissues. Mast cells were visualized by staining with acidic toluidine blue and by reaction with orthophthalaldehyde to develop histamine fluorescence. Although mast cells were easily identified in preparations such as canine liver, ear and scrotal skin and rat tongue, no such cells were found in any species (except the cow) in any part of the vascular wall. The results indicate that in most species histamine is stored in the vascular wall in a non-mast cell pool which may well be in the smooth muscle cells themselves.