The ontogeny of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the rat central nervous system was examined using the indirect immunofluorescence technique. Caudally located neurons displayed CGRP-LI relatively early in development. For instance, CGRP-immunoreactive (CGRP-IR) cells were first visualized in the hypoglossal nucleus and dorsal nucleus of the lateral lemniscus at day 19 of gestation, while by day 1 postnatal the facial and ambiguus nuclei possessed their full complement of immunoreactive neurons relative to that observed in the adult. By contrast, CGRP-IR somata in more rostral regions such as the lateral septal nucleus were not visualized until much later in development, i.e. day 12 postnatal. By day 15 postnatal, however, CGRP-LI was at a maximum in almost all areas scrutinized. This pattern of immunostaining persisted up to the oldest age studied (day 28 postnatal), except in the lateral septal and parabrachial nuclei, along the dorsal border of the medial lemniscus, and in the inferior olive, where many of the previously immunopositive cells could no longer be detected. In summary, CGRP-IR somata in the rat central nervous system appear in a principally caudal to rostal direction, beginning in late gestation. In some regions, CGRP is present only ephemerally. The ontogeny of CGRP during maturation of the rat brain is consistent with its suggested neurotrophic and neurotransmitter roles.