Transmembrane receptor-type protein tyrosine phosphatases (RPTPs) form a novel and potentially important class of cell regulatory proteins. To identify RPTPs expressed during neural development we have characterized RPTPs transcribed in embryonic day (E)13.5 rat neural tube. Nine different phosphatases, one of which was novel, were identified. We examined the expression of the novel phosphatase, called RPTP psi, and of two other phosphatases, RPTP delta and RPTP mu, whose expression in the developing nervous system has not yet been described in detail. The expression of RPTP mu in small blood capillaries in developing neural tissue is consistent with an involvement in angiogenesis. In contrast, the temporally and spatially regulated expression of RPTP psi and RPTP delta in neuroepithelium suggests a role in early neural development. In the spinal cord, early expression of RPTP delta in the roof plate is followed by its expression in differentiating motor neurons. RPTP psi mRNA is also transiently detectable in the roof plate as well as in floor plate cells. In the telencephalon as well as in the hindbrain at E13.5, the reciprocal expression patterns of RPTP delta and RPTP psi are consistent with a sequential function, RPTP psi exerting its activity in undifferentiated progenitor cells and RPTP delta functioning during neuronal differentiation.