Livers from male Sprague-Dawley rats were perfused with heparinised, unmodified isogeneic rat blood (n = 6) or xenogeneic human blood. The microcirculation of these livers, as the primary manifestation of hyperacute xenogeneic rejection, was directly observed and quantified by using fluorescence videomicroscopy. Bile flow and enzyme release of the isogeneic perfused livers were in the physiological range, whereas bile flow was significantly reduced and enzyme release increased during xenogeneic perfusion. In contrast to an almost physiological acinar (90.4%) and sinusoidal (93.6%) perfusion rate in the isogeneic group, a rapid breakdown of microcirculation with an acinar perfusion index of 47.5% and a sinusoidal perfusion rate of 67.1% were found in the xenogeneic group. This direct quantification of microcirculatory parameters is a step forward towards sensitive and early characterisation of the severity of the xenogeneic rejection of the liver.