Diabetes affects the structural and functional integrity of many organ systems, including the gastrointestinal tract. It has been demonstrated that diabetes is associated with spontaneous gastric ulceration, and enhanced susceptibility of the gastric mucosa to injury. However, the intracellular events that regulate these processes are poorly understood. In light of our observation that in healthy adult rats, acute gastric mucosal injury results in a marked induction in EGFR tyrosine kinase (Tyr-k) activity (Histol. Histopathol. 12: 491-501, 1997), we compared gastric mucosal EGFR Tyr-k between streptozotocininduced (50 mg/kg; i.v.) 3-month old diabetic rats and their healthy counterparts. The gastric mucosa was analyzed 3 weeks after induction of diabetes, when blood glucose concentrations were between 300 and 400 mg/dL. Results revealed a 40-50% higher EGF-R Tyr-k activity in the gastric mucosa of diabetic rats than in their healthy counterparts. This was accompanied by a 400-600% increase in the relative concentration of EGFR as well as the extent of tyrosine phosphorylation of the receptor and other proteins. Recent results from this laboratory suggest that the membranebound TGF-ct may play a critical role in regulating EGFR Tyr-k activity in the gastric mucosa (Am. J. Physiol. 273: G389-G398, 1997) through a autocrine/juxtacrine mechanism. To determine whether a similar mechanism may also be responsible for the induction EGFR Tyr-k in the gastric mucosa of diabetic rats, mucosal membrane and cytosolic fractions were analyzed for TGF-ot levels by Western-immunoblot. We observed that the relative concentration of the 14 kDa precursor form of TGF-ct in gastric mucosal membranes, but not in the cytosol, was 600-700% higher in diabetic rats when compared with the corresponding preparations from their healthy counterparts. Our results demonstrate that diabetes produces a marked increase in EGFR Tyr-k activity in the gastric mucosa, which could partly be the result of increased production of the enzyme and/or a greater accumulation of TGF-tx in mucosal membranes. Supported by grants from the NIH/NIA