Lung transplantation is an accepted modality for patients with cystic fibrosis (CF) who have end-stage respiratory failure. The postoperative course of these patients is often complicated by serious infections with organisms such as Pseudomonas aeruginosa and Pseudomonas cepacia that may be multiply resistant to conventional antimicrobial agents. We describe two patients with CF who, after double lung transplantation, developed the unusual complication of empyema and empyema necessitatis due to P cepacia that was resistant to all tested antibiotics.