SummaryThe major variation in effect between undiluted cystic fibrosis and heterozygote sera on rabbit tracheal epithelium was in terms of the time after exposure at which changes occurred. Exposure to both types of sera for 3 min caused release of goblet cell mucus and ciliary resorption possibly by apical swelling of columnar cells. Fusion of cilia and loss of microtubule pairs increased markedly through 60 min exposure. After 60 min exposure to heterozygote sera, a thick mucus net formed over many regions of the ciliary surface trapping cilia. Cilia from these areas showed separation occurring between adjacent pairs of peripheral microtubules with individual microtubule pairs remaining intact. Prolonged exposure (60 min) to cystic fibrosis serum resulted in increased mucus secretion and massive columnar cell loss. Some columnar cells were extensively swollen and basal cells showed significant changes. Control serum had no effect on tracheal epithelium over the same time span. Such cystic fibrosis serum-induced changes are characteristic of what one would expect from cells undergoing extensive cytolysis and are much more severe than those induced by heterozygote sera.SpeculationA component in cystic fibrosis serum may alter membrane regulation resulting in increased levels of intracellular calcium in ciliated and goblet cells. This increase may account independently for ciliary alterations and mucus secretion which ultimately cause ciliary dyskinesia. Prolonged calcium influx may account for the cytolysis of epithelial cells. Comparable factors may be responsible for mucus stagnation and respiratory dysfunction in patients with cystic fibrosis.