A time sequential study was performed to investigate the histological and ultrastructural findings of fumonisin B₁-induced apoptosis in the male Sprague-Dawley rat liver. Six hours after administration of FB₁, marked morphologic changes of hepatocytes included the appearance of small vacuoles along the margin of cell membrane. Twelve hours after injection of FB₁, acidophilic degeneration of cells occurred, but no fragmented nucleus was evident around the centrilobular area, with few apoptotic cells. By electron microscope, the degenerated acidophilic cells revealed following changes: characteristic formation of cytoplasmic vacuoles, condensed cytoplasm, detachment from neighboring cells, and as well as margination of nuclear chromatin and swollen mitochondria with amorphous matrical deposit. The number of apoptotic cells or bodies was further enhanced at 24 hours in the vicinity of dense acidophilic cells, resulting in a marked increase over the values of control rats. Serum analysis revealed the elevation of cholesterol levels from the beginning to the end of this experiment. Morphologic data and serum findings in this study support the theory that FB₁-induced alteration of membrane lipid constituents of the hepatocytes are likely to be early key events in explaining the FB₁ apoptotic effect.