The DNA sequence of a clustered set of genes which are conserved in orthopoxviruses has been determined for the avipoxvirus, fowlpox virus. The arrangement of the genes in fowlpox virus is nearly identical to that in vaccinia virus, and genes which are overlapping in vaccinia virus overlap in fowlpox virus. One major difference exists however, as the thymidine kinase (TK) gene is absent in fowlpox virus from the position it occupies within this cluster of genes in vaccinia virus. Instead, in fowlpox virus there is a 32 bp non-coding region present between the genes that flank the TK gene in vaccinia virus. The fowlpox virus TK gene has been cloned and sequenced. The sequences immediately flanking the TK gene show no homology to any previously reported poxvirus gene. These results are discussed in terms of genome stability in poxviruses and the use of the TK gene as a non-essential region for the introduction of foreign genes into poxviruses.