Mucosal disease can be experimentally induced by inoculating calves persistently viremic with noncytopathogenic (ncp) Bovine Virus Diarrhea Virus (BVDV) with an antigenetically closely related cytopathogenic (cp) BVDV strain. Calves suffering from mucosal disease develop severe intestinal lesions causing breakdown of the gastrointestinal barrier and death. Knowledge about tissue distribution of ncp/cp biotypes of BVDV may contribute to the understanding of the pathogenesis of these lesions. Distribution of cpBVDV versus ncpBVDV was demonstrated in the intestinal tract of nine calves with experimentally induced mucosal disease and in five persistently viremic calves. Biotypes were distinguished immunohistochemically in organ tissues using monoclonal antibodies against marker epitopes on the viral surface glycoprotein gp53. In persistently viremic calves ncpBVDV was present in a few epithelial cells, mononuclear cells and intramural ganglia. A multifocal reaction was observed in vascular walls. In calves with mucosal disease a striking increase of antigen containing cells occurred. Viral antigen in these cells reacted with marker antibodies for cpBVDV. A distinct tissue distribution of biotypes was observed in intramural ganglia and duodenal glands. Severe tissue damage was correlated to the presence of cpBVDV antigen. This indicates the importance of cpBVDV for the development of lesions. Interactions of cpBVDV and immunemediated mechanisms will need further investigation.