We have examined gastrointestinal mucosal growth 30 days after surgical removal of the submandibular-sublingual salivary glands and ligation of the parotid ducts of rats. The rate of [3H]thymidine uptake in vitro as an estimation of DNA synthesis and the content of DNA and RNA were examined in the oxyntic, duodenal and proximal colonic mucosa. DNA synthesis, DNA and RNA content of oxyntic mucosa were reduced in sialoadenectomized rats when compared to sham-sialoadenectomized control animals. There was no change in the degree of [3H]thymidine incorporation or DNA content of the duodenal or colonic mucosa. Intraperitoneal injection of an aqueous extract of the submandibular-sublingual salivary glands of rats (4.0 mg tissue protein in 0.1 M-sodium phosphate buffer administered twice a day for 15 days) increased the rate of DNA synthesis and the total mucosal DNA and RNA content in the oxyntic mucosa. Injections of extracts of spleen or muscle did not produce consistent results. Administration of epidermal growth factor (10 micrograms/kg) or pentagastrin (250 micrograms/kg) resulted in an increase of the level of DNA synthesis observed in the oxyntic mucosa of sialoadenectomized rats. Plasma and antral tissue levels of the trophic hormone, gastrin, were not significantly decreased in sialoadenectomized rats treated with 0.1 M-sodium phosphate-buffered saline. However, treatment with the salivary tissue extract did result in significant reductions in both plasma and tissue levels of gastrin. We conclude that elimination of the major salivary glands in the rat results in a decrease in [3H]thymidine uptake and DNA content of the gastric oxyntic mucosa. These effects are not mediated via a reduction in endogenous levels of the trophic hormone, gastrin. Administration of an aqueous extract of salivary tissue exerted a small but significant trophic influence on the oxyntic mucosa of the rat.