In this study, the expression of receptors for calcitonin (CTR), the CTR C1a and C1b isoforms, was investigated during development of the fetal rat central nervous system (CNS) by using in situ hybridization and immunohistochemistry. Coincident expression with both techniques was evident. Immunohistochemical evidence for the expression of the C1a isoform alone was found. Expression was first observed at embryonic day 12/13 (E12/E13) within and adjacent to the ventricular zones known to include primary matrices of proliferation, in regions of the preoptic area, anterior and posterior hypothalamus, anterior and posterior pons, medulla, and spinal cord. At later times, with the decline in the density of immunoreactivity at these loci (E15), expression in primary matrices was found later at distinct loci within the ventricular zones of cerebellum (E17), and at E19, the tectum, lateral ventricle, and cortical subplate. By E19, the density of staining had increased and was widespread throughout the expanding CNS. In the rostral domains, moderate to high density was found in the external plexiform layer; the medial preoptic area and nucleus; the ventromedial, dorsomedial, and arcuate hypothalamic nuclei; and the lateral and posterior hypothalamic areas. In the midbrain, similar levels of expression were noted in the central nucleus of raphe; the deep mesencephalic, dorsal raphe, and laterodorsal tegmental nuclei; and the ventral periaqueductal gray. In the pons, positive loci included the locus coeruleus and the gigantocellular and pontine reticular nuclei. In the medulla, high expression was evident in the gigantocellular, intermediate, magnocellular, and medullary reticular, spinal trigeminal and cuneate nuclei; and the nucleus tractus solitarius. In the spinal cord, moderate to high density of staining was found in the ventral, dorsal, and lateral horns, and in the ventral, dorsal, and cuneate funiculi. On the other hand, transitory expression was found in the diagonal band, bed nucleus of the stria terminalis, amygdala, and the lateral mamillary and anterobasal nuclei of the hypothalamus. These studies indicate a role for CTR in the activation of some premigratory neuroblasts in the CNS as well as a possible role later in an undefined function associated with mature neurons of particular nuclei.