Antisense nucleic acids against specific sequences of mouse hepatitis virus (MHV)-RNAs were tested for their inhibitory effects on viral multiplication in mouse DBT cells. An antisense oligonucleotide containing a sequence complementary to leader RNA was synthesized and shown to induce a significant inhibitory effect on the multiplication of MHV-JHM. A vector which expressed the antisense or sense mRNA7 of MHV was transfected into DBT cells. A decreased multiplication of MHV was observed in both cell lines. The transfected cell line which expressed ribozyme against the 5'-end of the MHV genome was established. The rate of inhibition of MHV-multiplication and the quantity of synthesized virus-specific mRNAs in this transfected cell line were the same for both antisense and sense RNA. These results show that antisense nucleic acids might be eligible for use as antiviral agents against MHV multiplication.