Four adult cystic fibrosis patients were selected for aggressive surgical management of sinus disease on the basis of severe pulmonary involvement, high frequency of hospital admission, chronic headache, and wheezing unresponsive to conventional treatment. They underwent bilateral Caldwell-Luc procedure with perioperative anti-Pseudomonas antimicrobials. There were substantial improvements in headache and respiratory symptoms and a significant reduction in the frequency of hospital admission after the operation. These findings suggest that sinus disease is associated with pulmonary exacerbation in patients with cystic fibrosis, and strengthens a similar observation in patients with asthma.