Transforming growth factor a (TGFa) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGFa/EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGFa mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGFa mRNA was also detected in matched surgically resected gastric mucosa and adjacent gastric carcinoma from 10 patients, and in gastric mucosa adjacent to a benign ulcer from an additional patient. TGFa protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGFa/EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGFa and TGFa/EGF receptor mRNA expression was examined in samples of unfractionated guinea pig gastric mucosa and from chief cell-enriched and parietal cell-enriched fractions. All samples exhibited TGFa and TGFa/EGF receptor expression. The TGFa signal was greatest in the parietal cell fraction (5.8-fold increase), but was also enhanced in the chief cell fraction (1.9-fold increase) relative to the unfractionated gastric mucosa. Like TGFa expression, TGFa/EGF receptor mRNA expression was most intense in the parietal cellenriched fraction (7.8-fold increase), but was also increased in the chief cell-enriched fraction (2.7-fold increase) relative to the unfractionated guinea pig gastric mucosa. We conclude that TGFa and TGFa/EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGFa and EGF, provide evidence that local production of TGFa could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.