An animal model permitting study of congenital infections with cytomegalovirus (CMV) has been developed in guinea pigs. Fifteen Hartley strain guinea pigs in the latter half of pregnancy were inoculated intraperitoneally with 10(5.5) 50% tissue culture infective doses of guinea pig CMV. Forty percent of infected mothers delivered litters containing at least one infected newborn, as defined by a positive culture of lung, spleen, or brain. All tissues were cultured by an explant technique. The three mothers who had no detectable complement-fixing antibody to CMV prior to experimental infection delivered infected litters, whereas three of 12 immune mothers delivered infected litters (P less than 0.01). A low-passage, tissue culture-adapted virus produced neonatal infection as frequently as did salivary gland-passaged virus. No congenital abnormalities were found in any of the seven infected newborns. CMV was isolated from lung, spleen, or brain in the four newborns of nonimmune mothers; CMV was isolated from lung only in the three newborns of immune mothers. These preliminary experiments demonstrate that the guinea pig is a suitable animal for further study of maternal-fetal CMV infections.