As shown in a previous study, intragastric administration of 16,16-dimethyl prostaglandin E2 (PGE, 100 micrograms/kg t.i.d.) for three weeks induces growth of the gastric mucosa. The present experiments were designed to study the time course of histological changes after intragastric PGE and to test whether a similar effect could be observed after parenteral administration. Significant thickening of the corpus, but not the antral mucosa was observed after 3 days of intragastric treatment with PGE (100 micrograms/kg t.i.d.), whereas after three weeks the effect was more marked in the antrum than in the corpus. At a dose of 25 micrograms/kg t.i.d., intraperitoneal PGE increased the height of antral mucosa to a similar degree as seen after intragastric treatment. DNA synthesis as assessed by autoradiography after administration of 3H-thymidine at the end of the three week PGE treatment was increased both in the gastric corpus and antrum. Preliminary studies in suckling rats provide evidence that intragastric administration of PGE (100 micrograms/kg t.i.d.) from day 7 to 11 accelerates maturation of the gastric mucosa. It is concluded that thickening of gastric mucosa can be induced by both local and systemic administration of PGE and is due, at least in part, to increased proliferation of gastric mucosal cells.