SummaryThe importance of intracellular calcium (Ca) in secretion and transmembrane ion movement led us to study Ca in cells from patients with cystic fibrosis (CF) which is a lethal genetic exocrinopathy. Skin fibroblasts from patients with CF, obligate heterozygotes (HZ), and age- and sex-matched controls (C) were used in matched pair experiments measuring45Ca exchange into and efflux from the cells over time. CF cell lines and HZ cell lines exhibit increased45Ca exchange when compared with their respective controls (P< 0.005). The magnitude of this difference (approximately 30%) is not reduced when cells are washed with lanthanum chloride after the exchange period. This difference is likely attributable to an altered capacity of one or more of the intracellular Ca sequestering organelles. Further evidence for this explanation was seen in46Ca efflux experiments in which CF cells retained a higher percent of their initial 0-time45Ca than did C cells late in the efflux period (P< 0.05). The finding of an altered Ca pool size in both CF and particularly HZ cells suggests that altered Ca metabolism is related to the basic gene defect in CF.SpeculationIncreased intracellular Ca in CF cells, while necessarily secondary to the basic gene defect, may influence cellular metabolism sufficiently to be a basis for many events in the pathogenesis of the disease. The presence of the Ca pool size alteration in cells from obligate heterozygotes is evidence that this phenomenon is closely related to the basic gene defect.