Compositions and methods for modulating the effects of cytomegalovirus (CMV) infections are disclosed, comprising contacting CMV mRNA with an oligonucleotide which can bind with at least portions of the CMV RNA. In accordance with the preferred embodiments, oligonucleotides such as ISIS 2922 are designed to bind with portions of the CMV mRNAs which code for the IE1, IE2 or DNA polymerase proteins. In accordance with a preferred embodiment, methods of treatment of human cytomegalovirus are disclosed.