The gubernaculum guides inguino-scrotal testicular descent by migrating into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) is present in the genitofemoral nerve of the neonatal rat and stimulates gubernacular motility in vitro. In a previous study in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. Binding analysis using computerized densitometry revealed a single class of sites. This study aimed to characterize the ontogeny of CGRP receptors in the gubernaculum and their response to denervation. Gubernacular sections from neonatal male rats were incubated with [125I]human CGRP as well as a variety of unlabeled neuropeptides. The expression of CGRP receptors culminates during the first week after birth, when gubernacular migration actually occurs. Significantly higher binding capacities were found in the denervated gubernacula compared with those in controls, which suggests an upregulation of CGRP receptors as a result of the genitofemoral nerve denervation. These results are consistent with the hypothesis that CGRP released from the nerve acts directly on the developing cremaster via its own receptors, which have not been described previously in this tissue.