To elucidate mechanisms underlying gap junction-mediated intercellular communication in epidermal keratinocytes, we have examined the expression of four connexin genes, Cx26, Cx31.1, Cx37, and Cx43, in fetal (embryonic day 17-18), newborn (post-natal day 0), and mature rat skin. Northern analyses of total skin RNA showed that levels of Cx26, Cx37, and Cx43 mRNAs remained relatively constant throughout the three developmental stages examined, whereas Cx31.1 mRNA was 15-30 times more abundant in mature skin than in fetal skin. Antibodies specifically recognizing these connexin proteins were then used in conjunction with a recently described amplification technique to immunohistochemically stain sections of paraffin embedded rat tail epidermis. We show that Cx26, Cx31.1, Cx37, and Cx43 display overlapping but distinct patterns of expression within the keratinocyte cell layers of developing and mature epidermis.