Respiratory disease is a common cause of morbidity in the guinea pig, and is chiefly of bacterial origin [6, 71. Although a variety of viral diseases do occur in the guinea pig, there has been only one previous report of cavian respiratory disease associated with what was believed to be an adenovirus [6] and none reported in the U.S. We report here two cases of pneumonia associated with a virus morphologically similar to adenovirus.Two adult, female Hartley Crl:(HA/BR) guinea pigs being used in anthrax vaccine trials showed clinical signs of hunched posture, weight loss, rough hair coat, rapid labored breathing, and a catarrhal exudate around the external nares and on the front feet. Guinea pig 1 had received five injections of an experimental anthrax vaccine at two-day intervals, while guinea pig 2, as part of the control group, had received five saline injections at the same intervals. Of the other 1 18 guinea pigs in the experiment, three had died prior to this small outbreak but were not submitted for histological examination.Guinea pig 1 died six days after the fifth injection. Guinea pig 2 was moribund and was killed the same day. Gross necropsy findings were similar for both guinea pigs. A catarrhal exudate was found throughout the entire upper respiratory tract and formed a brown crust around the external nares. All lung lobes remained partially distended with well-delineated, variably-sized reddish foci. The left caudel lobe of guinea pig 1 was markedly reddened over much of the lobe. No other significant gross lesions were noted. Aerobic bacterial cultures of lung, liver, and middle ears had no growth. No pathogenic species were isolated from bacterial cultures of proximal tracheal and pharyngeal swabs.The lungs were perfused via the trachea with 10% buffered formalin and then immersed with other samples of all organs in the same fixative. Organ sections were embedded in paraffin, sectioned at 6 Fm, and stained with hematoxylin and eosin (HE).Several I-mm' pieces of lung containing bronchioles were selected under a dissecting microscope, post-fixed in 1% OsO, in phosphate buffer, dehydrated in an ethanol series, and embedded in epon. Sections were cut and stained with uranyl acetate and lead citrate. and examined on an electron microscope at 80 kV.Histologic examination revealed that bronchial and bronchiolar lumens were occluded with necrotic debris and sloughed epithelial cells ( fig. la, Ih). While the majority of bronchioles had no viable epithelium remaining (fig. la), others had intact or hyperplastic epithelial cells ( fig. Ih). Both sloughed and intact epithelial cells had large basophilic intranuclear inclusion bodies: the sloughed cells were more prominent. The peribronchiolar stroma was infiltrated densely with lymphocytes, macrophages, and occasionally neutrophils. The lung parenchyma contained foci of alveolar septa1 thickening due to proliferating lining cells and infiltration of macrophages, lymphocytes, and a few neutrophils. Numerous small to extensive areas of congestion could be seen...