SummaryThe effect of high-protein pyridoxine-deficient diet on the localization of lysosomes and acid phosphatase activity in the rat liver was studied using light and electron microscopy. Numerous lysosomes con taining lipid droplets appeared to arise directly from GERI (Golgi apparatus, endoplasmic reticulum and lysosomes) near bile canaliculi and thereafter large crystal clefts were frequently found in these lysosomes. The increased appearance of lysosomes in hepatocytes was compatible with increased lipid droplets and represented an indication of breakdown of stored lipids. Acid phosphatase activity was localized almost exclusively in lysosomes with or without lipid droplets. We postulated that one of the causes of accumulation of lipid in hepatocytes, including that of tri glyceride and cholesteryl ester, might be associated with a relative deficiency of intralysosomal digestion in these conditions.