The relative abundance of mRNAs encoding the gamma- and epsilon-subunits of acetylcholine receptor changes in opposite directions during mouse development. Both gamma- and epsilon-mRNAs are expressed early in muscle development in vivo, and in aneural embryonic muscle and myogenic cell lines in vitro, though gamma-mRNA is at least 20-fold more abundant than epsilon-mRNA in these circumstances. While during normal development, gamma-mRNA decreases to an undetectable level by postnatal day 12, epsilon-mRNA first increases 10-fold between day 2 and day 12-15, then decreases to the level characteristic of adult muscle. We have found that the transition form gamma- to epsilon-mRNA is influenced by the levels of thyroid hormones. Indeed, high and low levels of thyroid hormones, respectively, accelerated and delayed the switch between gamma- and epsilon-mRNAs. Neither the dramatic postnatal rise in epsilon-mRNA nor its sensitivity to thyroid hormones was observed in denervated newborn animals. By contrast, denervation was without effect on epsilon-mRNA expression in adult muscle. These results suggest that, although not required for the initial activation of the epsilon-gene nor its maintenance in adult muscle, the nerve plays a major role in the perinatal regulation of epsilon-gene transcription.