Twenty-four patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) were followed in a double-blind placebo-controlled trial to assess the effect of ranitidine 300 and 600 mg daily on upper gastrointestinal mucosal damage and to assess methods of monitoring mucosal damage. Sixteen were given ranitidine and 8 had placebo throughout the study. Comparisons suggested that ranitidine reduced symptoms and endoscopic evidence of mucosal damage. Histological evidence of gastritis was present in only half of those on ranitidine but in all receiving placebo. Erosions and blood loss occurred intermittently during the study but faecal blood losses using 51Cr-labelled red cells failed to identify any difference between groups. Endoscopic observation of erosions and serial biopsies may provide simple, reliable measurements for future studies to assess the effect of therapy in reducing mucosal damage from long-term NSAIDs.