Neurosteroids are steroids that are synthesized de novo in the brain and include some classical (adrenal and gonadal) steroids and some unique brain-specific steroids. Neurosteroids are thought to mediate their action through ion-gated channel receptors, such as gamma-aminobutyric acid(A) and N-methyl-D-aspartate rather than through classical nuclear steroid hormone receptors. Some enzymes involved in neurosteroidogenesis have been identified as those found in steroidogenic tissues, and some may be unique to the brain. We previously demonstrated that the messenger RNAs for the cholesterol side-chain cleavage enzyme, P450scc, and one form of 11 beta-hydroxylase, P450c11 beta, are regionally expressed in the adult rat brain. We now demonstrate that P450scc is expressed in the nervous system of the developing rodent embryo in cell lineages derived from the neural crest. Despite the presence of readily detectable P450scc protein, a ribonuclease protection assay detected P450scc messenger RNA only in the trunks and not in the heads of male and female rat embryos. P450scc immunoreactive protein is continuously expressed in the central and peripheral nervous systems from embryonic day 9.5 in the rat. The sites of expression of P450scc are located mainly in sensory structures of the peripheral nervous system during embryogenesis, suggesting a possible function in coordinating environmental cues and behavior and in the development and organization of the nervous system.