In situ hybridization and virus titration were used to characterize ea
rly stages of rat virus (RV) infection of rat pups after oronasal inoc
ulation. Results suggest that virus enters through the lung and that e
arly viremia leads rapidly to pantropic infection. Cells derived from
all three germ layers were infected with RV, but those of endodermal a
nd mesodermal origin were the predominant targets. Infection of vascul
ar endothelium was widespread and was associated with hemorrhage and i
nfarction in the brain. Convalescence from acute infection was accompa
nied by mononuclear cell infiltrates at sites containing RV DNA. Viral
DNA was also detected in endothelium, fibroblasts and smooth muscle m
yofibers four weeks after inoculation. Further examination of these ce
lls as potential sites of persistent infection is warranted.