The 1983-base pair nucleotide sequence of the EcoRI-HindIII fragment of vaccinia virus Tiantan strain HindIII K clone is determined by the dideoxy chain termination method. A search in the NBRF protein sequence database using FASTA and other microcomputer programs reveals that several proteins belonging to the serpin (serine protease inhibitor) superfamily have striking similarities to the protein encoded by the HindIII K1 ORF. On the basis of the dot-matrix analysis and sequence alignment, the K1-encoded protein is shown as a novel member of the serpin superfamily. The putative reactive site and switch sequence of this novel serpin are then compared with those of other serpins. The probable evolutionary and possible functional relationships are discussed.