African Swine Fever (ASF) may lead to death of infected pigs or to a chronic carrier state. ASF virus generally enters the body through the mouth and infects the tonsils and mandibular lymph nodes, where it rapidly multiplies. Spread from initial foci of replication leads to a primary viremia which occurs 8-12 hours post-inoculation. By 15-24 hours post-inoculation, the virus spreads to the spleen and liver, giving rise to a secondary viremia.' By 30 hours post-inoculation, most tissues contain virus. The highest titers are found in primary-infection tissues. The early appearance and rapid increase of virus in the spleen, liver, lungs, and lymph nodes suggest that the tissues are sites of secondary virus replication. In highly vascularized organs, this may be due more to the amount of blood contained than to replication of the virus in the t i~s u e .~ Using immunofluorescent techniques, the highest concentrations of fluorescent cells have been found in lympho-reticular organs1 although fluorescent cells are also in pulmonary and hepatic parenchyma cells. In the liver, fluorescence was only found in some small, elongated Kupffer cells in the sinusoids, while in other pigs fluorescence was detected in large, oval, mononuclear cells located both in the sinusoids and in the hepatic cells. Lesions in the liver in acute ASF include congestion, cellular infiltration of interlobular connective tissue, hepatocyte degenerati~n,~ and degeneration of Kupffer cell^.^^^ Necrosis occurs both in individual hepatocytes and in groups of hepato~yte.~.~ Cells infiltrating interlobular connective tissue include eosinophils, mononuclear cells, lymphocytes, plasma cells, and histio~ytes.~-'~ In this study, nine male, large, white, cross-landrace pigs were divided into three groups: two animals from each group received intramuscular inoculation of 5 x los HA,, ASF virus (strain E70, supplied by I.N.I.A. of Madrid); one pig was a non-infected control. Pigs were killed with azaperone at 3 (group I), 5 (group 11), and 7 (group 111) days after inoculation. The liver was fixed by perfusion in 2.5% glutaraldehyde in 0.1 M phosphate buffer; samples of hepatic parenchyma were embedded in paraffin, glycol-metacrylate, and araldite. For direct immunofluorescence (DIF) tests, an anti-African swine fever virus (anti-ASV) serum, together with fluorescein isocyanate with a titer of between 1/75 and 1/ 100, obtained from pigs inoculated intramuscularly with attenuated ASF virus was used. For ultrastructural study, 60 nm sections were cut and stained with uranyl acetate and lead citrate, and examined in an electron microscope.Lesions in livers of pigs with ASF consisted of degeneration and necrosis of Kupffer cells and hepatocytes. There was evidence of viral replication sites in both types of cells. Vascular alterations consisted of congestion and edema, and a large number of mononuclear cells in sinusoids and interlobular spaces.At 3 and 5 days post-inoculation, hypertrophic Kupffer