The synthesis of herpes simplex virus (HSV) in mouse neuroblastoma cells (NB, clone 41A3) is restricted. There was a disappearance of infectious virus upon serial passage of infected cells. NB cells treated with sodium-n-butyrate for 24 hr before infection synthesized 200-2000 times more HSV than untreated cells. Infectious center assays demonstrated that the number of cells capable of producing HSV was increased as a result of butyrate pretreatment. Although host protein synthesis was inhibited by HSV infection, viral-induced protein and DNA syntheses were not detected in the absence of butyrate. Cycloheximide blocked the induction of permissiveness by butyrate suggesting that a protein(s) was responsible for allowing HSV synthesis in NB cells. Regulatable host factors involved in HSV replication in neural cells can be studied in the system described.