We constructed cDNA libraries from a clonal human teratocarcinoma-derived cell line and two retinoic acid-induced derivatives: a homogeneous population of neurons and a FACS-isolated, non-neuronal population. These libraries are large and representative of the cells from which they were derived, as determined by colony hybridization. PCR analysis indicates that the transcripts encoding P- and E-cadherin are down-regulated whereas the the prion protein (PrP) transcript is up-regulated in neurons. These cells offer a promising system for investigations of human prion infection and the cDNA libraries provide a source of neuron-specific genes.