AbstractSevere acute respiratory syndrome (SARS) is a new human infectious disease with significantmorbidity and mortality. The disease has been shown to be associated with a new coronavirus(SARS-CoV). The clinical and epidemiological aspects of SARS have been described.Moreover, the viral genome of SARS-CoV has been fully sequenced. However, much of thebiological behaviour of the virus is not known and data on the tissue and cellular tropismof SARS-CoV are limited. In this study, six fatal cases of SARS were investigated for thetissue and cellular tropism of SARS-CoV using an in-situ hybridization (ISH) technique.Among all the tissues studied, positive signals were seen in pneumocytes in the lungsand surface enterocytes in the small bowel. Infected pneumocytes were further confirmedby immunofluorescence–fluorescence in-situ hybridization (FISH) analysis. These resultsprovide important information concerning the tissue tropism of SARS-CoV, which is distinctfrom previously identified human coronaviruses, and suggest the possible involvement ofnovel receptors in this infection. Whereas the lung pathology was dominated by diffusealveolar damage, the gut was relatively intact. These findings indicated that tissue responsesto SARS-CoV infection are distinct in different organs. Copyright 2004 John Wiley &Sons, Ltd.