The interactions in vivo between Plasmodium berghei sporozoites and Kupffer cells in rat livers were studied by transmission electron microscopy. By 10 and 15 min after inoculation, sporozoites were both free in the liver sinusoids and inside endocytotic vacuoles of the Kupffer cells. The latter cells were very active in phagocytosing sporozoites, bacteria and red blood cells. The sporozoites retained their integrity inside the endocytotic vacuoles and no signs of lysosomal digestion were observed. Sporozoites seen within endocytotic vacuoles 1 h after inoculation were still morphologically intact, although bristle-coated vesicles fused with the vacuole membrane. Evidence is presented which suggests that Kupffer cells transport sporozoites towards the space of Disse and adjacent hepatocytes. No sporozoites were seen to penetrate an endothelial cell or its narrow fenestrae. It is proposed that Kupffer cell passage, rather than gaps in the sinusoidal lining, represents the normal route that sporozoites take to circumvent the endothelial barrier. The localization of exo-erythrocytic forms was made easier by the use of Brown Norway rats in which many more parasites develop than in the Wistar rats. The distribution pattern of the parasites was found to be mainly around the 'periportal' zones of the acini of liver tissue.