The pathogenetic role of non-steroidal anti-inflammatory drugs (NSAIDs) in peptic ulcer disease is reviewed, on the basis of available experimental and epidemiological knowledge. In addition, original clinical data are provided concerning the prophylactic and therapeutic role of the H2-receptor antagonists ranitidine and cimetidine, and colloidal bismuth subcitrate, in the treatment of NSAID-associated peptic lesions in rheumatic patients.