The transcription factor SRF is involved in the transduction of extracellular signals into nuclear responses, often in conjunction with ternary complex factors (TCFs). Here we report the identification of CArG box SRF binding-sites, and neighboring TCF binding-sites, in viral genomes. SRF binds and recruits TCFs to CMV, RSV and HTLV-1 viral genomes. At least one of two specific CArG boxes occurred in cytomegaloviruses in the 5' proximal region of the major immediate early gene, one always accompanied by a TCF site. This conservation was striking since neither the flanking sequences nor the spacing to the CAP site were conserved. Thus the ubiquitous SRF and TCF molecules may control events in the life cycle of viruses.