C1300 mouse neuroblastoma cells are nonpermissive for infection with herpes simplex virus owing to a failure of viral immediate-early gene transcription following infection. The weak activity of the immediate-early gene promoters in these cells is mediated by the binding of a repressor factor to the octamer-related TAATGARAT motifs in these promoters. This repressor activity is specific to cells of neuronal origin (being absent in a range of permissive nonneuronal cells) and is also able to repress the activity of cellular octamer-containing promoters introduced into C1300 cells. The role of this repressor in the regulation of octamer-containing cellular genes in neuronal cells and in the control of latent infections with herpes simplex virus is discussed.