Two woodchucks (Marmota monax) intrahepatically inoculated with hepati
tis delta virus (HDV) complementary DNA clones pSVL-D3 and pSVL-Ag sho
wed virological and pathological signs of acute and chronic HDV infect
ion. HDV-RNA and hepatitis delta antigen (HDAg) were detected in serum
by slot-blot hybridization and by western blot five weeks after inocu
lation. Liver biopsy specimens collected at 8th week post inoculum wer
e positive for HDV-RNA. Anti-HDV antibodies were detected at the 11th
and 9th weeks, respectively. Histological finding of hepatocarcinoma a
nd persistence of circulating HDV-RNA and anti-HDV were observed up to
the 10th month. Both woodchucks produced ''small'' and ''large'' HDAg
antigen, although the inoculated cloned DNA bears the coding capabili
ty solely for the small antigen. A transient decrease of woodchuck hep
atitis virus DNA (WHV-DNA) level was observed during the peak of HDV i
nfection. Successive inoculation of acute-phase serum in three woodchu
cks resulted in a successful infection in one of the animals.