Immunohistochemical analysis with the anti-Ret antibody was performed to investigate the expression of the c-ret proto-oncogene product (c-Ret protein) in embryonic, infant and adult rat tissues. During embryogenesis, the c-Ret expression became detectable by day 11.5 in the developing peripheral and central nervous systems as well as in the excretory system. In the peripheral nervous system of the trunk, it was expressed at high levels in the enteric neuroblasts and the autonomic and dorsal root ganglia. c-Ret positive cells appeared in the mesenchyme around the foregut and the dorsal aorta at day 11.5 and formed the myenteric plexus of the whole embryonic gut and the sympathetic trunk at later stages respectively. Examination of the cranial region revealed that the c-Ret protein was expressed in neural crest cells migrating from rhombomere 4 at day 11.5 and then became positive in the facial, glossopharyngeal and vagus cranial ganglia at day 12.5-13.5. After day 16.5 of gestation, the c-Ret expression was also observed in the trigeminal ganglion. In the central nervous system, the c-Ret protein was expressed in the neuroepithelial cells of the ventral neural tube (day 11.5-14.5), the motor neurons of the spinal cord (day 18.5) as well as in the embryonic neuroretina (day 18.5). In addition to the nervous system, the c-Ret expression was detected in the nephric duct (day 11.5), the ureteric bud (day 13.5) and the collecting ducts of the kidney (day 16.5). After birth, neurons in the nervous systems mentioned above continued to express the c-Ret protein at variable levels while no c-Ret expression was observed in the kidney of adult rats. Furthermore, the c-Ret expression was found in the acinar cells of the salivary gland, the epithelial cells of the thymus and the follicular dendritic cells of the spleen and lymph node in infant and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)