By comparing sets of variola virus (VARV) genomes and sets of vaccinia virus (VACV) genomes, it was found that the insertion and deletion of small pieces of DNA (3-25 nucleotides) were common events among these poxviruses. Insertion events were characterized by the creation of tandem direct repeats, whereas the deletion events generally took place between two direct repeats that were separated by a few nucleotides. A number of the VARV and VACV indels clearly did not fit the expected phylogenetic tree patterns. Some of these were found to be the result of coincident events, but others, in VACV, suggest recombination among the VACV genomes. Such recombination would make the construction of phylogenetic trees problematic. The growth of VACV under artificial conditions and at high multiplicities does not select against these deletions.