Mouse primordial germ cells (PGCs) are migratory until they colonize the genital ridges, assemble with the somatic tissue, and start to differentiate into oocytes or spermatogonia. Using cell transplantation experiments, we show here that germ cells isolated during migration (at E10.5) will migrate actively to the genital ridges, whereas post-migratory PGCs isolated from E12.5 embryos are non-motile even when transferred into a permissive environment (e.g. E10.5 host tissue). Major transcriptional changes must take place between E10.5 and E12.5 that convert germ cells from a migratory to a non-migratory state. To identify the genes involved, we have performed transcriptional profiling of motile and non-motile populations of PGCs. We have identified 55 transcripts that are expressed in E10.5 PGCs at levels at least 3 x their expression at E12.5, and 48 transcripts with the reciprocal expression levels. Additionally, 309 transcripts were found to be expressed in both populations. Many of the E10.5 transcripts encode proteins involved in controlling cytoskeletal and adhesive interactions implicated in cell motility. Many of the E12.5 transcripts encode proteins implicated in germ cell differentiation.