To study the role of herpes simplex virus type 1 immediate-early proteins in the transcriptional activation of herpes simplex virus genes, we isolated stably transformed cells expressing herpes simplex virus type 1 ICP4, an immediate-early protein known from previous studies to be necessary for delayed-early and late transcription. These cells efficiently expressed six delayed-early herpes simplex virus genes introduced by viral superinfection, in the absence of de novo viral protein synthesis. In contrast, the delayed-early gene encoding alkaline exonuclease and the late gene encoding the capsid protein VP5 were expressed at much lower levels. Expression of a second late gene, that for glycoprotein C, was undetectable under the same experimental conditions. These results suggest that many, but not all, delayed-early genes are efficiently activated by ICP4; in addition, they demonstrate that although the late gene for VP5 is detectably activated by ICP4, its full expression requires additional factors.