The Epstein-Barr virus BRLF1 and BZLF1 genes appear to be the first viral genes transcribed upon induction of the Epstein-Barr virus lytic cycle. Both gene products activate transcription of other viral genes, thereby initiating the lytic cascade. Among the viral antigens expressed upon induction of the lytic cycle, the product of the BZLF1 gene is unique in its ability to disrupt viral latency; thus, expression of this gene is both necessary and sufficient for triggering the viral lytic cascade. Moreover, transcription initiation from both the BRLF1 and BZLF1 promoters can be activated by the BZLF1 gene product. The latter results suggest a two-step model for induction of the viral lytic cycle in which the initial signal leads to low-level transcription of the BZLF1 gene, followed by upregulation of transcription by the BZLF1 gene product. In this report we demonstrate that efficient transcription from the BRLF1 and BZLF1 promoters after anti-immunoglobulin induction of the lytic cycle, in a synchronous induction system, is dependent on de novo protein synthesis. These data support the two-step induction model in which synthesis of BZLF1 protein is required to activate expression of the BRLF1 and BZLF1 genes.