Ten healthy men participated in a crossover study, and the experiments took place after 10 days of treatment (40 mg omeprazole every morning). Blood samples were drawn at fixed intervals during a complete migrating motor complex (MMC) cycle. The manometric pressure tube was removed after passage of the second duodenal phase III, and an omelet (1400 KJ) tagged with 99mTc was ingested, followed by 150 ml of water tagged with 111In-diethylenetriaminepentaacetic acid. Mean plasma gastrin (pmol/l) in phases I, II, and III in the omeprazole group was 18.8, 23.3, 19.9, respectively. The corresponding figures for the placebo group were 9.3, 9.6, 9.5, respectively. All mean values for the omeprazole group were significantly higher (p less than 0.01). Mean plasma gastrin in the omeprazole group was significantly higher in phase II than in phase I (p less than 0.05). Mean plasma secretin (pmol/l) in phases I, II, and III in the omeprazole group was 1.6, 1.4, 1.1, respectively. The corresponding figures for the placebo group were 2.0, 1.7, 2.2, respectively. Mean plasma secretin in the omeprazole group was significantly lower in phases I and III (p less than 0.05). The mean incremental integrated postprandial gastrin response (pmol.30 min/l) was significantly higher in the omeprazole group (475.0 versus 97.5) (p less than 0.05). The immediate postprandial mean value of secretin was significantly lower in the omeprazole group (p less than 0.05). We conclude that 40 mg omeprazole elicits i) a phase-related increase in fasting plasma gastrin, ii) a decrease in secretin in phases I and III, iii) an augmented meal-stimulated gastrin response, and iv) a secretin response characterized by a significantly lower mean in the immediate postprandial period.