The mammalian Krüppel-like transcription factors are key regulators of multiple morphogenetic programs. Here, we examined the developmental expression of the mouse Klf5 gene and compared it to the established pattern of the Klf4 gene. The results revealed that the two genes are expressed in both overlapping and mutually exclusive patterns. Unlike Klf4, Klf5 mRNA is detected in the E15.5 meninges and in the E.16.5 epithelium of trachea and bronchi. Both genes are co-expressed in the outer layer of the tongue, as well as in the developing epidermis and gut with interesting temporal differences. Klf4 expression in the skin gradually decreases from E15.5 on, whereas Klf5 transcripts continue to accumulate at a fairly high rate in the basal layer of the epidermis. The same sustained activity of Klf5 is already seen in the gastrointestinal tract of the 10.5 day embryo, and is later confined to the base of the intestinal crypts. Maximal Klf4 expression in the gastrointestinal tract is limited to a narrower window of time during the late phase of development.