The Herpesviridae are a family of viruses which have a large genome of linear, 
double-stranded DNA (> 120 kb). It has been quite difficult to clone and modify 
herpesvirus genomes because of their large sizes. Recently, several groups of 
investigators demonstrated successful cloning of infectious herpesvirus genomes 
as bacterial artificial chromosomes (BACs). In this review, I describe the 
recent development of methods to modify the cloned viral genomes. The methods 
are: (i) homologous recombination in E. coli which allows targeted mutagenesis 
of any specific viral sequence, and (ii) mutagenesis which allows random 
modification of entire viral genomes. Both methods should facilitate both the 
study of herpes viruses and the development of herpesvirus-based vector system.