The multiple pathogenic effects of human cytomegalovirus (HCMV) result from a complex interplay of viral gene products and induced and repressed cellular functions. HCMV immediate early and early gene expression clearly play a pivotal role in this scheme. I describe here work directed at elucidating the sequence requirements and trans-acting factors necessary for the activation and regulation of HCMV early genes. The focus is on three transcription units which are all activated at early times, but exemplify differential patterns of expression as the infection progresses, including: the major 2.7- and 1.2-kb transcripts encoded by the repeat bounding of the long unique segment of the genome, and a family of differentially spliced transcripts (originally designated the 2.2-kb RNAs-ORF UL112-113) which encode four proteins that are required in the transient complementation assay for HCMV DNA replication. Selected other early genes which illustrate alternative mechanisms of control are also discussed.