We report two siblings with cystic fibrosis and systemic amyloidosis. The major clinical problem in both cases was recurrent respiratory infection with pulmonary fibrosis and bronchiectasis prior to death at ages 20 and 22 years. Findings from postmortem examinations disclosed diffuse amyloidosis. In addition, amyloid infiltration developed in both patients, with enlargement of the thyroid gland, and one required thyroidectomy. An autopsy review of 17 additional cases of cystic fibrosis failed to disclose any other instances of systemic amyloidosis.