Multivesicular lysosomes were observed by electron microscopy in 25 of 41 liver biopsies of subjects with various diseases. These organelles were acid phosphatase positive and were limited by a single membrane with a homogeneous electrondense crescent and contained numerous lipidlike particles of different sizes reminiscent of lipoproteins. The lesion was seen in both alcoholic and nonalcoholic liver injury, and was negatively correlated p < 0.0001 with hepatic vitamin A: all 18 patients with a hepatic vitamin A level below 80 μg/g had the lesion, whereas only 1 of 11 subjects with a hepatic vitamin A concentration higher than 160 μg/g displayed multivesicular lysosomes. Unlike its association with low vitamin A level in the liver, the lesion could be seen even in the presence of normal serum values of vitamin A, retinol binding protein, and prealbumin. The relationship between the lowered hepatic vitamin A and multivesicular lysosomes was then demonstrated in rats fed a vitamin A-deficient diet: all animals fed the vitamin A-deficient diet displayed the lesion, and addition of ethanol to the deficient diet increased its frequency. Feeding of a vitamin A-deficient diet was also associated with a lowered level of circulating very low density lipoproteins that was further decreased by the addition of ethanol. No multivesicular lysosomes were seen in rats fed a normal vitamin A containing diet (with or without ethanol). In conclusion, multivesicular lysosomes are found in a variety of liver disease states and they are associated with lowered hepatic vitamin A level.