The virus-coded proteins pIRS1 and pTRS1 were found associated with purified human cytomegalovirus virions. The proteins were not degraded when intact virions were treated with trypsin, which suggests that they are localized inside the viral particle. In transfection experiments pIRS1 and pTRS1 modestly activated expression from a reporter plasmid containing the viral major immediate-early promoter but did not influence the activity of a reporter carrying the irs1/trs1 immediate-early promoter. Both reporters were activated by the combination of pIRS1 or pTRS1 and pUL69, which is also present in virions.