Infection with mouse hepatitis virus-3 (MHV-3), a member of the coronavirus family, leads to a strain-dependent spectrum of liver disease. Mice of the BALB/cJ, C57BL/6J, and DBA strains are fully susceptible, exhibiting 100% mortality when infected with as little as 0.1 PFU of MHV-3, while A/J mice are resistant, as defined by complete survival and normal liver histology after infection with 2 X 10{sup 4} PFU. All of these strains are permissive for viral replication, suggesting that host immune factors, rather than viral cytopathology, are responsible for the observed difference in mortality. While the pathogenesis of MHV-3-induced liver disease is not fully understood, several lines of evidence indicate that local activation of the coagulation cascade prior to detectable viral replication plays an important role in liver cell injury. First, microscopy performed early in the infection of susceptible mice has shown sinusoidal thrombosis and foci of coagulation necrosis associated with varying degrees of inflammatory cell infiltration. Second, a correlation between disease severity and the induction of macrophage procoagulant activity (PCA) has been established, with susceptible mice developing an earlier and heightened PCA response relative to resistant strains. Finally, treatment of mice with a monoclonal antibody to MHV-3-induced PCA prevents the lethality associated with infection. Genetic linkage in the form of an identical strain distribution pattern was established between susceptibility to infection with MHV-3 and inducible macrophage PCA, using the set of AXB/BXA recombinant inbred strains derived from resistant (A/J) and susceptible (C57BL/6J) progenitors. 18 refs., 1 tab.