The experiments reported here allowed us to compare the metabolism of neutral lipids from extracellular origin (lipoproteins) and endogenous origin (triacylglycerol biosynthesis induced by feeding cells with high levels of free fatty acid) in normal and acid-lipase-deficient fibroblasts (Wolman's disease). When the cells were grown in hyperlipemic-rich medium, a major neutral lipid storage appeared in normal as well as in acid-lipase-deficient cells; this storage disappeared rapidly in normal cells during the 'chase', whereas in Wolman cells, the storage of cholesteryl esters and triacylglycerols remained unchanged, or only decreased very slowly. When the cells were fed with high levels of radiolabelled oleic acid, a major accumulation of radiolabelled triacylglycerols was observed. These cytoplasmic triacylglycerols were similarly degraded in normal and Wolman fibroblasts during the 'chase' period. From these results it was concluded that the neutral lipids stored in lysosomes of Wolman fibroblasts are only of extracellular origin (lipoproteins), whereas triacylglycerols biosynthesized by the cells do not participate in this accumulation. Therefore, both cellular compartments involved in triacylglycerol metabolism (lysosomes containing exogenous lipids and cytoplasmic granules of endogenously biosynthesized triacylglycerols) are strictly independent.