The effects of caerulein, vinblastine (VB), deuterium oxide (D2O), and cytochalasin B upon both the structure and the function of the pancreatic acinar cell were studied in vitro using rat pancreatic fragments. Caerulein (10 ng. per ml.) stimulates the release of enzymes and induces the appearance of numerous exocytotic images at the apical part of the acinar cell. Whereas VB (5.10(-5) M) and D2O (55 per cent) inhibit the secretory response to caerulein, they do not affect the general ultrastructure of the acinar cell. Prolonged incubation in the presence of VB provoked the disappearance of microtubles and the massive precipiation of microcrystalline material in all parts of the cytoplasmic space. Numerous microtubules were found in the acinar cell after exposure to D2O. Although VB and D2O do not alter the microfilamentous network localized at the apical part of the cell, cytochalasin B (2.10(-5) M) disrupts it. This drug decreases the number of microvilli projecting into the enlarged acinar lumen. Whether cytochalasin B is used alone or in association with VB or D2O, it inhibits the secretory response to caerulein and prevents the process of exocytosis. Thus, it is suggested that microfilaments act on a later step of the secretory cycle, i.e., exocytosis, than microtubules. The probable site of action of these latter organelles in the migration of zymogen granules toward the acinar lumen is discussed.