The experiments described deal with the histamine content of the different regions of the digestive tract, from the oesophagus to the rectum, and of the different layers of the wall at each region studied. Although various authors have described the presence of histamine in the wall of the digestive tract, a systematic survey of its distribution has so far not been attempted. The paper also includes preliminary experiments on the distribution of another smooth muscle stimulating substance which resembles the substance P of Gaddum & Schild, and may be identical with it.The results of previous work on histamine in the wall of the digestive tract may be summarized as follows: Histamine has been isolated chemically from gastric and intestinal mucosa of various species (Barger & Dale, 1911;Abel & Kubota, 1919), and under conditions which exclude the possibility of bacterial origin or the formation from putrefactive changes during the extraction (Gerard, 1922; Sacks, Ivy, Burgess & Vandolah, 1932). Schild's experiments (1939) on the guinea-pig's digestive tract indicate that histamine is present along its whole length. He found that histamine was released from the oesophagus, stomach, small and large intestine during the antigen-antibody reaction of anaphylaxis. Quantitative estimates of the histamine present in the wall of the intestine and stomach have been obtained by biological assay in various species. In the small intestine the values per gram of fresh tissue were for the horse 7-8,ug. (Gaddum & Schild, 1934), for the dog 35,ug. (Gaddum, 1936), and for the guinea-pig 8-5-20ig. (Schild, 1939). The values for the horse and dog were obtained after removal of the mucosa. The histamine present in the gastric mucosa has been determined by Gavin, McHenry & Wilson (1933), by Emmelin & Kahlson (1944), and by Trach, Code & Wangensteen (1944 5-34 (average 16), pyloric region 4-16 (average 9); human beings, fundus 4-24 (average 10), antral region 3-12 (average 6). Gavin et al. showed further that the muscularis propria contained, less histamine than the mucosa, which contains 80% of the histamine of the stomach wall. Histamine appears also in the gastric juice and is thought to be derived from the mucosa histamine (for references see Babkin, 1950).The name substance P was given by Gaddum & Sohild (1934) to an unknown substance found first by Euler & Gaddum (1931) in extracts of the muscle coat from the small intestine and of brain and believed to be a polypeptide. The extracts caused a fall of arterial blood pressure in the atropinized rabbit and a slow contraction of the isolated atropinized intestinal preparation of the rabbit. Euler (1934, 1936a) found large amounts of what appeared to be the same substance in human semen and in extracts of the prostrate gland of various animals. Substance P has a stimulating action on a number of smooth muscle preparations and on smooth muscles in vivo, but it has apparently no effect on the bronchi (Euler, 1936b;Bjurstedt, Euler & Gernandt, 1940;Gernandt, 1942; Vogt, 1949Vogt, , ...