The salivary gland virus of guinea pigs, or guinea pig cytomegalovirus (CMV), was first described in The Journal of Infectious Diseases in 1920. Early studies were concerned with the nature of intranuclear and intracytoplasmic inclusions, viral pathogenicity, transmissibility in animals, and similarity to human viral infections. Subsequently, tissue culture techniques and electron microscopy of guinea pig CMV-infected salivary gland and tissue culture cells demonstrated the morphogenesis which closely resembles that of human CMV. By use of tissue culture cocultivation techniques, generalized viremic infection, transplacental transmission of virus, congenital infection, CMV-associated mononucleosis, interstitial pneumonia, and transmission of virus by blood transfusion have been demonstrated. In studies of live attenuated and noninfectious envelope antigen vaccines for the prevention of transplancental transmission of virus and of interstitial pneumonia, the guinea pig model has demonstrated efficacy of such vaccines under experimental conditions. Investigations of polymorphonuclear leukocyte function during primary CMV infections may elucidate mechanisms for bacterial, parasitic, and fungal superinfections in human disease.