Protocadherin (Pcad) is a group of molecules obtained by polymerase chain reaction (PCR) utilizing the sequence that is well preserved in the extracellular domain of cadherin. Sano et al. analyzed Pcad (PC42,43) that had been cloned from rats, and found that it basically had homology to cadherin, but contained more than six cadherin repeats with a completely different intracellular domains (Sano et al. 1993). In the present study, of the Pcad (Pcad-1,2) cloned from a human cDNA library, as-yet-unspecified Pcad-2 was analyzed for expression in the human fetal central nervous system (CNS). Northern blot analysis of adult human tissue showed that Pcad-2 was expressed in the brain and the placenta, and that Pcad-2 mRNA was expressed in actively dividing neural tumor cell lines. Monoclonal antibodies against Pcad-2 were then made, and the CNS of fetuses were immunohistochemically stained. The expression was hardly visible at the 6th week of pregnancy, and began to become visible along the nerve fiber in the brain stem at the 8th week, and spread over the entire brain at the 11th week. At the 18th week, however, expression in the nerve fascicles, which had been visible by that time, was no longer visible or had decreased. These results suggest that Pcad-2 appears relatively early in the critical stage of development of the fetal CNS, and is involved in the induction, fasciculation, and extension of axons.