The purpose of the present report is to study the effects of antidepressants such as trimipramine, amitriptyline, maprotiline and mianserin on severe gastric mucosal lesions produced by ethanol in comparison with cimetidine (H2-antihistamine) and dexchlorepheniramine (H2-antihistamine). The percentage of macroscopic mucosal lesions caused by alcohol affects 15% of the mucosal area. But pretreated with cimetidine the affected area was 9.18%, with dexchlorepheniramine 5.01%, with trimipramine 14.46%, with amitripytline 7.94%, with maprotiline 3.8%, and with mianserin 4.07%. Microscopic evaluation reveals that ethanol produces destruction of glandular cells and injures medial and basal layers. All drugs used previously to ethanol produce a decrease of microscopical lesions. A direct relation was found between micro and macroscopical lesions in rats treated with maprotiline, mianserin and dexchlorepheniramine.