Monoamine oxidase was investigated histochemically in tissues of the mouse by incubating freeze-dried, whole-body sections with tryptamine, serotonin, tyramine, beta-phenylethylamine, or benzylamine as substrate and Nitroblue tetrazolium as the final electron acceptor. The most intense staining with tryptamine was exhibited by intestinal epithelium and adrenal cortex; moderate staining was noted in the epithelium of the nose, bronchi, oesophagus, and upper stomach and in preputial gland, pancreas, nerve, spinal cord and brain. Weak staining was seen in the lung, spleen, liver and kidney. The distribution of the formazan deposition was similar, but much less intense, when serotonin and tyramine were used as the substrates. Only very weak staining was observed when beta-phenylethylamine was the substrate; no staining was seen with benzylamine. Monoamine oxidase activities with tryptamine were greatly inhibited by pretreatment with clorgyline (10 microM), while deprenyl (10 microM) slightly inhibited activities in all tissues except liver. This staining technique should be useful in further studies on the identification of the multiple forms of monoamine oxidase in tissues of the mouse. Nicotine and nitrosonornicotine were not substrates in any of the tissues; consequently, this enzyme system does not appear to produce the proximal carcinogen from this nitrosamine.