Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the modulation of the inflammatory response. However, a number of facts involving the occurrence of gastrointestinal lesions have limited the chronic use of NSAIDs. In order to diminish the occurrence of gastrointestinal damage caused by NSAIDs, the combination of NSAIDs with the H2 receptor blocker, cimetidine, has been evaluated. The anti-inflammatory and ulcerogenic effects of indomethacin and tenoxicam in association with or without cimetidine were determined at pre-clinical levels. It was observed that the group of animals treated with indomethacin and cimetidine, or tenoxicam and cimetidine (10 mg/kg, p.o.) demonstrated a significant reduction (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test) of type-III gastric ulcers. Furthermore, indomethacin or tenoxicam (10 mg/kg, p.o.) in association with cimetidine increased the anti-inflammatory activity. The group, which received indomethacin and cimetidine presented the best performance in decreasing the inflammatory process (P < 0.05, ANOVA followed by Tukey-Kramer multiple comparison test).