Two guinea pigs (Cavia porcellus), which were housed conventionally in separate animal facilities and had not been experimentally manipulated, were found to have evidence of disseminated cytomegalovirus disease at necropsy. Microscopic examination revealed multiple focal areas of necrosis in numerous organs. The spleen, liver, kidney and lungs were affected particularly. These lesions contained numerous cells with large intranuclear and cytoplasmic inclusion bodies resembling cytomegalovirus inclusions. Characteristic cytomegalovirus virions were observed by electron microscopy in both cases. Antigens of guinea pig cytomegalovirus were detected in paraffin sections of lesions from both cases with an immunoperoxidase technique. Although subclinical infection is common, this is the only contemporary report of disseminated disease due to cytomegalovirus in guinea pigs.