Numerous viruses cause disease in vertebrates by selective infection of mucous membranes or by achieving entry to deeper tissues of the body through these membranes. Tropism for villous epithelium is characteristic of the viruses causing transmissible gastroenteritis in pigs and rotaviral diarrhea of calves while the feline panleukopenia virus characteristically infects and causes destruction of the rapidly proliferating cells of intestinal crypts. In contrast bovine viral diarrhea (BVD) virus is representative of viruses which cause lesions of extraintestinal tissues as well as the mucosa of the intestine apparently due to tropism for a variety of cell types;Infection of cattle with BVD virus results in lesions primarily in the lymphoid tissues and oral and gastrointestinal mucosa. Infection of leucocytes has been indicated further by suppressed in vitro and in vivo responses;Although considerable experimentation has been conducted with BVD virus, more information on the pathogenesis of the disease was needed. Of particular interest was the tropism of the virus for cells in intestinal tissue and the effect of the virus on the lymphoreticular system. The experimentation sought to evaluate pathologic and immunologic responses in the intestine of cattle which were infected with the virus by inoculation of fistulated or ligated segments of the ileum;Clinical observations of experimentally infected animals included diphasic febrile responses and leucopenia with an absolute reduction in lymphocyte and polymorphonuclear cells. Peripheral lymphocyte transformation indices were reduced in all infected animals but failed to show a consistent pattern for the period over which this influence was evident. Pathological changes observed by periodic intestinal biopsy included nonspecific responses of edema, hyperemia with extravasation of erythrocytes, villous atrophy and an increase in goblet cell numbers. This was succeeded by attenuation of the epithelial cell layer and infiltration of the lamina propria by mononuclear and eosinophilic leucocytes. Viruses were located by electron microscopy in epithelial cells and lymphocytes of Peyer's patches thus indicating viral tropism for these cells;Specific virus neutralizing antibodies were detected in intestinal secretions at 6-12 days following infection and coincided with increasing levels of IgA. Neutralizing antibodies were detected in blood serum 11-15 days postinoculation and subsequent to viremia;Although tropism of the virus for lymphoreticular tissues was confirmed, the virus did not prevent the induction of a specific local immune response. The production of local antibodies has a primary role in response to and recovery from disease of the mucosa.