Retrovirus genomes introduced into mouse zygotes by microinjection of cloned DNA, or into morula stage pre-implantation mouse embryos by infection with Moloney murine leukaemia virus (M-MuLV), became de novo methylated and were blocked in expression. No restriction of virus expression and no de novo methylation were observed when post-implantation mouse embryos were infected with virus. Efficient de novo methylation activity may be an important characteristic of gene regulation in early mouse embryos.