Growth responses to endogenous and exogenous gastrin were examined in the pancreas and gastrointestinal tract mucosa. Rats were either antrectomized to remove the primary source of endogenous gastrin or subjected to a sham operation. Three weeks after surgery, half of the antrectomized animals were injected ip with pentagastrin (250 microgram/day) four times per day. Injections were carried out for a week. Antrectomy resulted in serum gastrin levels approximately one third of normal. DNA synthesis and DNA and RNA content of the pancreas and oxyntic gland, duodenal, and colonic mucosa were significantly reduced by antrectomy. In each case, pentagastrin treatment restored DNA synthesis and RNA and DNA levels to normal. Significant decreases in pancreatic and colonic weights in antrectomized animals were also completely prevented by pentagastrin injection. These results indicate that endogenous gastrin has an important role in the regulation of pancreatic and colonic mucosal growth, in addition to its already established similar function in oxyntic gland mucosa.