Mousepox is a widely feared disease of laboratory mice that recently caused severe epizootics in the U.S.A. The proposed research will make comparative clinical, pathogenetic, and epizootiological observations in prototype inbred mice - BALB/c (susceptible) and C57BL/6 (resistant)-infected with 2 strains of the causative agent, ectromelia virus: a U.S. isolate known as the NIH-79 strain, and the well known Moscow strain. This comparison is essential to validate new approaches to the control and elimination of mousepox derived from studies of mice infected with the U.S. strain. The role of airborne transmission in the epizootiology of mousepox also will be assessed. Virological, pathological, and immunological markers in susceptible and resistant mice will be used to detect early events in infection of resistant mice. These experiments will use virus quantitation, immunohistochemical identification of lymphoid cell types, in in situ cellular responses and cytotoxic cell responses in vitro. Preliminary genetic studies will attempt to determine the genetic basis for resistance. Some of these studies anticipate the use of recombinant inbred strains for identification of genes governing resistance and susceptibility to mousepox. The results of this research will help to develop new approaches for detection, prevention and control of mousepox.