The effect of two doses of cimetidine, 400 mg at night and 400 mg bd, on the protection of in domethacin (50 mg tid) induced mucosal damage was evaluated in a double blind study in patients with acute musculoskeletal disorders. Endoscopic mucosal lesions were scored before and after five to seven days of treatment. One hundred and ninety one patients were endoscoped before the trial, 34 (17·8%) had >one erosion and were not recruited. Forty patients were excluded for noncompliance, or lost to follow up. At the second endoscopy, oesophageal, and fundic damage was negligible. Gastric and duodenal lesion score in patients treated with cimetidine 400 mg bd: 2.7 (0·5) (SE); n=42) was significantly lower (p<0·0122) than in placebo treated patients: 6-1 (0·9) (n=50) or in patients treated with cimetidine 400 mg at night 7·1 (0·8) (n=21). Cimetidine 400 mg bd provided significant protection for the duodenum, but its protection of antral mucosa did not reach statistical significance. There was no correlation between upper gastrointestinal symptoms and endoscopic findings.