Cytomegalovirus (CMV) is the most common congenital viral infection, but little is known about the protective immune mechanisms. The guinea pig (gp) model of congenital CMV was used to evaluate the effects of passive antibody given to pregnant dams on pup survival. Dams received three doses of high-titer gpCMV or control antibody on days -3, -1, and +7, or +1, +3, and +7, in relation to gpCMV challenge. gpCMV was inoculated in the late second to early third trimester at three different doses. Compared with controls, gpCMV antibody begun before gpCMV challenge significantly increased pup survival from 14% to 52%, 21% to 84%, and 51% to 77%, respectively, for the three challenge doses. gpCMV antibody started after viral challenge increased pup survival after only the lowest challenge dose (51% to 81%). Antibody did not protect against CMV infection of the pups. CMV antibody appeared to improve survival in congenital CMV infection but did not affect vertical transmission.