The nucleotide sequence of the 3'-end of the genomic RNA of human coronavirus OC43 (HCV-OC43) was determined from the cDNA clones of the intracellular virus-specific mRNAs. The nucleotide sequence and the predicted amino acid sequence of the main open reading frame (ORF), which represents the nucleocapsid (N) protein, were highly homologous to those of bovine coronavirus (BCV) Mebus strain. This ORF predicts a protein of 448 amino acids. Additional smaller ORFs are also present in a different reading frame. We have also determined the leader sequence present at the 5'-end of HCV-OC43 mRNAs by a primer extension study. This sequence is highly homologous to that of mouse hepatitis virus, particularly in the 3'-end of the leader sequence, which is postulated to be involved in the unique mechanism of leader-primed transcription. These data suggest that HCV-OC43 and BCV might have diverged from each other fairly recently and that the 3'-end of the leader sequence has significant functional roles.