This study examined the question as to whether 16,16-dimethyl prostaglandin E2 prevents bile-induced gastric mucosal damage in man. Damage was induced by intragastric instillation of a 10 millimolar taurocholate solution. DNA-shedding, gastric transmucosal electrical potential difference, and the outputs of potassium and urea in gastric washings were measured as indices of mucosal damage. DNA-shedding during gastric washings with saline was 0.24 mg/15 min +/- 0.05 SEM and rose to 0.46 +/- 0.08 (p less than 0.025) during washings with taurocholate. Potential difference dropped from -35.6 mV +/- 1.6 to -21.9 +/- 2.3 (p less than 0.005). Potassium output was increased from 0.21 mmol/15 min +/- 0.01 to 0.50 +/- 0.03 (p less than 0.005), and urea output was increased from 0.45 mmol/15 min +/- 0.09 to 1.33 +/- 0.21 (p less than 0.05). These changes could be prevented neither by 20 micrograms/100 ml of 16,16-dimethyl PGE2 instilled intragastrically 45 minutes prior to the start of taurocholate administration, nor by 10 micrograms/100 ml of 16,16-dimethyl PGE2 instilled prior to taurocholate plus 0.7 micrograms/100 ml given together with taurocholate. It is concluded that "cytoprotection" appears to depend on the nature of the damaging agent, and may not occur under some conditions which play an important role in the pathophysiology of gastric mucosal diseases.