1. The previous findings that N-methylhistamine and N-dimethylhistamine are more potent stimulators of gastric secretion than histamine have been confirmed in dogs with Heidenhain pouches or gastric fistulas.2. In cats with gastric fistulas, doses of N-methylhistamine of 0.25 or 0.5 mumole/hr produced 1.4-1.6 times as much HCl as equimolar doses of histamine.3. The maximal HCl outputs of dogs with Heidenhain pouches to histamine, N-methylhistamine, and N-dimethylhistamine were not significantly different, though lesser doses of the N-methyl derivatives were required to produce the maxima. At the one-half maximal level, N-dimethylhistamine showed a twofold greater potency than histamine.4. When given slowly or quickly via arteries supplying blood to the stomach of dogs or cats with gastric fistulas or via the artery to a Heidenhain pouch in a dog, 0.1-1.0 mumole N-methylhistamine or N-dimethylhistamine produced 4.1-13.9 times as much HCl as equimolar doses of histamine.5. Injection of histamine or N-methylhistamine via the portal vein in two dogs with gastric pouches stimulated less secretion of HCl than injection of the same doses via a systemic vein.6. The results allow the conclusion that N-methylhistamine and N-dimethylhistamine are more potent stimulators of acid gastric secretion than histamine in dogs and cats, particularly when delivered directly via the arterial route to the gastric mucosa, and support the prospect that N-methylhistamine or N-dimethylhistamine or both are natural chemostimulators of the parietal cells.