BALB/c mice were given vinblastine (Velbe), 40 and 200 mg/kg, or vincristine (Oncovin), 20 mg/kg, dissolved in saline as single intraperitoneal injections. Nontreated mice served as controls. Animals were killed 1, 2, 5, and 24 hours and 4 days after the drug administration and small pieces from the pancreas were processed for electron microscopy. Autophagocytotic activity increased 3 hours after the injection and at 5 and 24 hours there were large amounts of autophagic vacuoles containing altered cell organelles and membranous or amorphous debris in the acinar cells. Cell death and acinar atrophy were evident at later time intervals. It was concluded that the vinca alkaloids caused autophagy and degeneration in pancreatic acinar cells and that their inhibitory effect on pancreatic enzyme secretion might depend partly or solely on their cytotoxic action.