After acute ethanol ingestion in C,,B1/6 mice, phagocytic activity of Kupffer cells and hepatic microcirculation were examined by in uiuo and electron microscopy. A ratio of Kupffer cells that phagocytosed 0.8 pm fluorescent latex particles to sinusoids containing blood flow (number of Kupffer cellslnumber of sinusoids containing blood flow) was used as a measure of Kupffer cell phagocytic activity. Three hours after ingestion of 1 gm/kg ethanol, number of Kupffer cells/number of sinusoids containing blood flow increased in both periportal and centrilobular regions by 62% and 66%, respectively, and blood ethanol was no longer detectable. Ultrastructurally, activation of KC was evidenced by the presence of many pseudopodia and filopodia. Numbers of swollen endothelial cells were increased in both regions by 249% and 174%. Interruption of sinusoidal blood flow by leukocytes was aggravated in both regions by 127% and 167%. Thirty minutes and 3 hr after ingestion of 4 gm/kg ethanol, no significant increase in number of Kupffer cellsinumber of sinusoids containing blood flow was seen, although number of Kupffer cells were also activated as seen with electron microscopy. An increased number of swollen endothelial cells was observed in both regions by 100% and 71% by 30 min and by 200% and 384% by 3 hr. The interruption of sinusoidal blood flow by leukocytes was also increased (periportal = 161%, centrilobular = 196%) as were sticking or plugging leukocytes in sinusoids (periportal = 320%, centrilobular = 120%) by 3 hr. The diameter of centrilobular sinusoids was decreased by 3 hr. Latex particles and platelets were attached to the sinusoidal wall after both low and high dosing. These findings suggest that acute ethanol ingestion activated Kupffer cells and affected the functions of leukocytes, platelets and endothelial cells.