Three case histories illustrate the diagnostic dilemma encountered whenever a patient with CF who is receiving antibiotics is evaluated for abdominal pain. Although acute appendicitis with perforation and abscess formation is not a common complication of CF, it occurs more frequently than is generally appreciated. The large number of abdominal situations in CF which can cause pain confused with but not typical of acute appendicitis. The true underlying condition is further masked by the concurrent use of antibiotics for pulmonary infection. A higher index of suspicion is needed to rule out acute appendicitis in a patient with cystic fibrosis and abdominal pain. A greater awaremess of the possibility of occult appendiceal abscess may help to avoid this complication.