To characterize the tissue and developmental-specific transcriptional activity of the human calcitonin receptor (hCTR) gene in vivo, transgenic mice containing a 4.9-kb hCTR promoter/beta-galactosidase (lacZ) construct were generated. Between 8.5 and 10.5 days of development, lacZ-positive cells were observed on the lateral side of cervical and occipital level somites and in the lateral myotome. LacZ-positive cells also appeared to be migrating from the dermomyotome into the adjacent limb buds, suggesting that the hCTR promoter is active in hypaxial muscle progenitors. By 11.5-16 days of development, novel hCTR expression sites were identified that included limb buds, cornea, retina, skin, intercostal muscles, muscles of the limbs, face, and dorsal root ganglion. hCTR promoter activity in a number of these tissues was repressed at adult stages of development, RT-PCR demonstrated endogenous mCTR mRNA in all lacZ-positive tissues assayed. The developmental regulation of hCTR gene expression in the above tissues suggests that CTRs are likely to play an important role in their morphogenesis.