The mammalian POU-domain factor Brn-3.0 (Brn-3, Brn-3a) is a member of the POU-IV class of transcription factors which resemble the C. elegans factor unc-86 in structure, DNA-binding properties and expression in subsets of sensory neurons. Using specific antisera, we have explored the expression of Brn-3.0 in the early development of the mouse nervous system. Brn-3.0 expression begins at embryonic day 8.5 (E8.5) in a specific set of midbrain tectal neurons whose time and place of appearance are consistent with the earliest CNS neurons previously identified using non-specific markers of neural differentiation. By E9.5, Brn-3.0 immunoreactivity also identifies early CNS neurons in the hindbrain and spinal cord. In the peripheral sensory ganglia, Brn-3.0 expression is first observed at E9.0 in migrating precursors of the trigeminal ganglion, followed by the other sensory cranial and dorsal root ganglia, in a rostral to caudal sequence. Double-label immunofluorescence with Brn-3.0 and the markers of cell division PCNA and BrdU demonstrate that Brn-3.0 is restricted to the post-mitotic phase of CNS development. In the sensory cranial and dorsal root ganglia, however, Brn-3.0 is expressed in dividing neural precursors, suggesting that the nature or timing of developmental events controlled by Brn-3.0 are distinct in the CNS and peripheral neurons. Restriction of Brn-3.0 expression to post-mitotic CNS neurons demonstrates that Brn-3.0 is not required for neurogenesis or patterning of the neuroepithelium in the CNS, but suggests a role in specification of mature neuronal phenotypes.