Basal and food-stimulated gastrin were measured in 16 patients with duodenal ulcer before and during long-term maintenance therapy with 400 mg cimetidine twice daily. Basal gastrin (mean +/- SE) rose significantly from 27.5 +/- 3.1 pmol/liter precimetidine to 32.8 +/- 2.1, 37.2 +/- 2.6, and 38.5 +/- 3.3 pmol/liter at 1, 3, and 6 months, respectively. The total integrated gastrin response to a protein meal was 1.67 +/- 0.18 nmol/liter/120 min pre-, and 2.54 +/- 0.35, 3.29 +/- 0.3, and 4.36 +/- 0.4 nmol/liter/120 min at 1, 3, and 6 months, respectively. These increases were significantly higher at each time period. This study has thus demonstrated a progressive increase in both basal and food-stimulated gastrin during cimetidine therapy, and this increase could theoretically lead to an increase in gastric acid secretion following cessation of cimetidine.