1. The effect of cholecystokinin octapeptide (CCK-8) and pentagastrin on periodic pancreatic secretion was studied in fasting conscious dogs. 2. Both CCK-8 and pentagastrin, in small doses, prolonged the interval of periodic pancreatic secretion. Periodicity was disrupted by large doses of CCK-8 and pentagastrin. 3. CCK-8, at the dose which did not disrupt the cycle, raised the peak and the valley-to-valley means, but not the valley mean, of protein secretion in one cycle. Except at large doses, pentagastrin failed to increase the peak and valley mean, but increased mean, valley-to-valley protein secretion. Large doses of both pentagastrin and CCK-8 increased protein secretion at the valley. 4. The peak of periodic pancreatic protein secretion was about half the observed maximum protein response to CCK-8. 5. Atropine reduced pancreatic fluid and protein responses to small doses of CCK-8 to the levels of valleys. At large doses, however, both responses were augmented by atropine. Hexamethonium reduced the responses to any dose of CCK-8 to valley levels or less. Volume and protein responses to pentagastrin following atropine or hexamethonium were of similar magnitude to those at valleys. 6. It is concluded that CCK-8 and pentagastrin stimulate pancreatic enzyme secretion directly by acting on acinar cells and indirectly by modifying cholinergic ganglionic activities which control periodic secretion in conscious dogs.