Acute pyloric ligation in the rat (Shay rat preparation) has been found to increase both gastric histamine formation from histidine decarboxylase (HDC) enzyme activity and total cellular histamine content of these stomachs. The peak elevation in gastric HDC activity (twelve-fold) and in gastric cellular histamine content (two-fold) occurred four hours postligation, with return to essentially normal levels for both by 24 hours postligation. This period of peak elevations was the approximate time of peak increases in gastric secretion in volume and acidity observed by others in the Shay rat. In the interval between four and 24 hours, gastric HDC remained somewhat elevated above normal levels and gastric histamine concentration was somewhat depressed below normal levels. Subcellular gastric concentrations of histamine were increased in the mitochondrial and supernatant fraction, decreased in the microsomal fraction, and unchanged in the nuclear fraction.