The role of subcellular organelles in the synthesis, transport, and secretion of pancreatic digestive proteins has been well documented. This study was designed to examine effects of pentagastrin, secretin, and acute and chronic administration of cholecystokinin-pancreozymin (CCK-PZ) on pancreatic macromolecular transport and secretion. Pooled rat pancreas slices were pulse-labeled with L-[14-C]phenylalanine and migration of 14-C-labeled proteins studied by "chase" incubation for 15, 30, 60, and 120 min. After in vitro incubation of control and drug-treated pancreatic slices, subcellular particles were isolated by differential centrifugation; Specific activity of radioactive labeled proteins was determined in subcellular fractions involved in transport and secretion of digestive proteins. These studies indicate that pentagastrin and acute and chronic stimulation with CCK-PZ did not alter the rate of transport of labeled proteins from ribosomes to the zymogen granules. Pentagastrin and CCK-PZ stimulated secretion of labeled proteins from the zymogen granules into the medium in the concentrations used as evidenced by significant increase in the amount of labeled proteins in the medium and significant decrease in the specific activity of the zymogen granule fractions after 60- and 120-min periods of incubation. Secretin did not alter the rate of transport or secretion of the pulse-labeled proteins.