1. Expression of the immediate early genes c-fos, c-jun and c-myc in rat stomach in response to feeding and gastric distension was examined by Northern blot analysis and in situ hybridization. 2. Refeeding of fasted rats induced a transient increase in c-fos mRNA abundance in gastric corpus and antrum that was sixfold within 15 min and declined within 4 h. The response was not mediated by gastrinergic or muscarinic cholinergic mechanisms; it was reduced but not abolished by hexamethonium. No changes in expression of c-jun, c-myc or the constitutively expressed protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were observed. 3. In conscious rats prepared with a gastric fistula, gastric distension with nutritive and non-nutritive solutions at a physiological pressure for 30 min induced expression of c-fos, c-jun and c-myc, but not GAPDH. 4. Messenger RNA encoding c-fos was localized by in situ hybridization to gastric myenteric neurones of animals that underwent gastric distension, but not of undistended controls. 5. The results suggest that expression of c-fos in gastric myenteric neurones is an early response to the physiological stretching of the stomach wall that accompanies feeding. With supraphysiological distension, other immediate early genes may be recruited.