Helicobacter-like organisms as well as fermentative bacteria have been implicated in gastric ulcer production in swine. Irregular feeding schedules are also considered a major risk factor. A research trial was conducted to determine whether medication with an acid secretion inhibitor (lansoprazole), either alone or in combination with an antibiotic (azithromycin), would protect pigs from gastric ulceration if the animals were subjected to a 48 h period of fasting. In a 2 x 3 factorial design, 48 pigs were fasted, while an equal number were fed ad libitum. Within these 2 study groups, pigs were randomly assigned to 1 of 3 treatments: control, 30 mg lansoprazole s.i.d. for 7 d, or lansoprazole (30 mg s.i.d. for 7 d) and azithromycin (500 mg s.i.d. for 3 d). Overall, fasted pigs were 1.9 times more likely to develop erosive or ulcerative lesions of the pars esophagea (chi2 = 9.89, P < 0.002). Treatment with an acid secretion inhibitor alone or in combination with an antibiotic did not protect pigs from developing gastric lesions. Helicobacter-like organisms were not detected in any of the stomachs. Possibly, the lansoprazole dose of 30 mg given once per day was insufficient to prevent pH levels from becoming low enough to cause damage to epithelial tissue. Alternatively other substances such as bile acids may have caused the ulcerative lesions, even though stomach acid production was suppressed.