A retrospective study of 90 infants and young children with cystic fibrosis and 90 age matched controls without cystic fibrosis revealed no essential histologic differences in their tracheobronchial mucous gland reactions with and without pulmonary infection. Although the secretory response to specific stimuli (especially Pseudomonas or staphylococcal infection) varied in individual cases, every change seen in cystic fibrosis was present in the controls. Inactive or normally active mucous glands were usually present in the cystic fibrosis and control infants in the absence of infection. Moderate mucous gland activity in the absence of overt infection was not pathognomonic of cystic fibrosis; it was seen in both groups in response to an irritative stimulus, such as aspirated blood or gastric contents. Mucous gland secretions contained both acid and neutral mucins in the presence of infection, with no real distinction between the cystic fibrosis infants and controls, differing from the predominantly acid mucins in infected polyps of older children. Reparative squamous metaplasia in the tracheobronchial tract occurred more frequently in infants with cystic fibrosis than in controls. Although cystic fibrosis did predispose to progressive pulmonary disease (bronchiolitis, bronchiectasis), similar lung lesions were found in other metabolic and chronic disorders.