Four infants with newly diagnosed cystic fibrosis developed a bulging anterior fontanel within days of starting enzyme replacement treatment. In the same time period, 41 hospitalized patients less than 1 year of age were diagnosed as having cystic fibrosis and treated, suggesting that increased intracranial pressure is common in this setting (9.7%). The clinical course of the four infants was similar: the bulging fontanel became apparent 1-6 days after initiation of pancreatic enzyme replacement and resolved within 1 week in three patients and within 4 months in the other patient. Two patients became mildly irritable. Computed cranial tomography and lumbar puncture were done in three patients, with completely normal findings except elevated cerebrospinal fluid pressure in two infants. There was no apparent difference in this treatment or clinical course before diagnosis between the four infants who developed a transient bulging fontanel compared with the overall group of cystic fibrosis patients.