Fibroblasts were cultured from skin biopsies of normal donors and cystic fibrosis (CF) patients, and compared morphologically and cytochemically by light and electron microscopy. Normal and CF fibroblasts revealed by light microscopy a comparable number of cytoplasmic bodies which contained acidic complex carbohydrate and acid phosphatase. These increased in prevalence with the number of days in culture, the time in culture between the last passage and assay, and the percentage of noncycling cells. The fibroblasts did not exhibit extensive or intense metachromasia. Normal and CF cells displayed similar fine structural morphologic features, including a comparable population of dense bodies. These contained acid phosphatase and became labeled by ferritin pinocytosed from the medium. The dense bodies were thus identified as secondary lysosomes engaged, at least in part, in the degradation of endocytosed material. The CF and normal cells exhibited no difference by light microscopy in reactivity to stains for neutral, sialic acid-rich, and sulfated complex carbohydrate. By electron microscopy, no difference in the content of acid complex carbohydrate was demonstrable with dialyzed iron. The amount and distribution of antimonate-precipitable cations was observed ultrastructurally and found to be similar in CF and normal cells. By morphologic or cytochemical criteria, it was not possible to distinguish CF from normal cells or to provide a basis for the extensive cellular metachromasia observed by some investigators in CF cells examined by light microscopy.