Ultrastructural and cytochemical observations indicate that both cystic fibrosis (CF) sera and calcium ionophore A23187 induce a swelling or an increase in the size and possibly the number of secondary lysosomes and an increase in mucus secretion in epithelium of the rabbit tracheal bioassay system. Extended incubation of the rabbit tracheal explants with either CF or control sera produces a cytotoxic effect on the tracheal epithelium, but only after the termination of the normal bioassay time period. Comparative ultrastructural study of the effect of both CF sera and calcium ionophore A23187 on the rabbit tracheal bioassay system indicates that increased membrane permeability to calcium may be important in the production of the ciliary dyskinesia response by CF serum factor(s) in the rabbit tracheal bioassay system.SpeculationCF serum factor(s) may be acting on the cultured rabbit tracheal explant epithelial membranes to produce altered membrane permeability to ions and to calcium in particular. This alteration in membrane function may be promoting the observed ultrastructural changes in the epithelial cells which include a swelling or increase in the number and size of secondary lysosomes and an increase in mucus secretion as well as ciliary dyskinesia. Alterations in membrane function and permeability may be related to the pathophysiology of this genetic disorder.