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A comparison of the effect of bombesin, dermorphin and salmon calcitonin on gastric acid secretion was assayed in rats two hours after their intracerebroventricular or subcutaneous administration. All three peptides significantly reduced gastric acid output after central administration. The order of potency was: bombesin greater than salmon calcitonin greater than dermorphin. After subcutaneous injection salmon calcitonin was very potent in reducing gastric acid output, while dermorphin was active only at high doses; bombesin had a very weak effect on the same parameter. Time-course studies demonstrated that the effect of these peptides reached a peak 1-2 h after their central administration, followed by a slow recovery toward control values. Salmon calcitonin, however, has a very prolonged action on the gastric parameters studied. These data indicate that bombesin and dermorphin might act centrally to modulate gastric acid secretion in the rat, while the very potent intracerebroventricular and subcutaneous action of salmon calcitonin suggests a different mechanism of action.