Pancreatic disease has been infrequently reported in patients with acquired immunodeficiency syndrome. Over the last 3 years at our hospital, two patients with the acquired immunodeficiency syndrome and acute pancreatic or biliary disease, demonstrated at autopsy to be secondary to cytomegalovirus infection of the pancreas, have been evaluated. However, pancreatic disease was not recognized antemortem in our two patients because of their underlying diseases and the atypical presentation. Cytomegalovirus infection of the pancreas may cause acute symptomatic disease in patients with acquired immunodeficiency syndrome.