Repetitive DNA elements account for a substantial fraction of the mammalian genome. Many are subject to DNA methylation, which is known to undergo dynamic change during mouse germ cell development. We found that repeat sequences of three different classes retain high levels of methylation at E12.5, when methylation is erased from many single-copy genes. Maximal demethylation of repeats was seen later in development and at different times in male and female germ cells. At none of the time points examined (E12.5, E15.5, and E17.5) did we see complete demethylation, suggesting that methylation patterns on repeats may be passed on from one generation to the next. In male germ cells, we observed a de novo methylation event resulting in complete methylation of all the repeats in the interval between E15.5 and E17.5, which was not seen in females. These results suggest that repeat sequences undergo coordinate changes in methylation during germ cell development and give further insights into germ cell reprogramming in mice. (C) 2003 Elsevier Science (USA). All rights reserved.