Map/Erk kinase 1 (MEK1) and MEK2 activate the Erk/ MAP kinases and have been implicated in cell growth and differentiation. To investigate the role of MEKs during mouse development, we have examined their expression and activity in various murine tissues during embryonic development and in the adult mouse. MEK2 RNA message is expressed at high levels in all embryonic tissues examined, including all neural tissues, and liver. This can be observed by in situ hybridization of tissue sections of 14.5-day-old mouse embryos, as well as by Northern blot analyses. MEK1, on the other hand, is expressed at very low levels in most embryonic murine tissue but can be detected in developing skeletal muscle. It is expressed at higher levels in adult tissue, particularly in brain, where it is expressed at high levels. Western blot analyses of MEK1 and MEK2 in 14.5-day-old embryonic and adult mouse tissue confirm the RNA analysis. Levels of MEK1 kinase activity are particularly high in adult brain tissues as well. These findings suggest that MEK2 may be the primary Erk/MAP kinase activator during development and that MEK1 may play a role in the proliferative or mitogenic response in adult mouse tissues. This study also raises the possibility that MEK1 and MEK2 might not have redundant functions in cells but may possess unique specificity in their interactions with upstream activators or downstream targets.