The time course of degradation of a radiolabelled natural ceramide has been studied in intact, living lymphoid cells and skin fibroblasts from normal individuals and from patients affected with Farber disease, an inborn disorder of ceramide metabolism due to deficient activity of lysosomal ceramidase. The hydrolysis of ceramide in lysosomes was selectively followed by examining the turnover of an LDL-associated radioactive sphingomyelin. This permitted to estimate accurately the effective lysosomal ceramidase activity and to demonstrate: (i) a very active catabolism of ceramide in normal cells; and (ii) the absence of a complete block of ceramide degradation in Farber cells. The possible implication of ceramide as a lipid mediator of the pathogenesis of Farber disease is discussed.