Histamine methyltransferase (HMT) activity was determined by a modified isotope assay in biopsy specimens from gastric mucosa of control subjects, duodenal ulcer patients and after various gastric operations. Enzymic activity of male control subjects who were 'healthy' with respect to their upper gastrointestinal tract was 70.4 +/- 12.8 pmol/(min x mg protein). In male duodenal ulcer patients HMT-activity was significantly lowered by 15%; following selective vagotomy with pyloroplasty a significant increase of 14% was observed as compared to controls. The difference between values before (59.9 +/- 13.3) and after (80.4 +/- 11.7) this operation was highly significant (p less than 0.001). Experiments in a small number of patients showed that after other modifications of vagotomy elevated HMT-activities were also found, whereas after resection procedures such changes of enzymic activity did not occur. According to these results the low gastric HMT-activity of duodenal ulcer patients could play a role in the pathogenesis of a chronic peptic ulcer by being responsible for reduced histamine inactivation and - as a consequence - enhanced acid secretion. Furthermore, vagotomy seemed to influence acid secretion in human subjects not only by direct effects on the parietal cells, but also by an activation of histamine catabolism. One patient, who despite complete vagotomy showed both no reduction in acid secretion and a low gastric HMT-activity, may be the representative of a new population of peptic ulcer patients.