Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We have used electron microscopy and morphometry to perform a qualitative and quantitative examination of lipid-storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. In parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increased in the total number of lipid vesicles in stellate cells in all PBC patients when compared with livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell in sizes of 1 microm to 5 microm in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid storage that involves stellate cells in PBC that could be an early manifestation of this disease. Its significance remains to be elucidated.