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Four hundred eighty house mice (Mus musculus) were trapped primarily from urban sites in Baltimore, Maryland from 1984 to 1989 and tested for antibody to lymphocytic choriomeningitis virus (LCMV). The majority of mice (95%) were trapped in residences at two city locations (n = 260), or in an urban park (n = 196); five additional sites were sampled. Overall, 9.0% of the mice were LCMV antibody positive and infected animals were obtained from six of eight sites, including all three of the primary city sites, where the prevalence varied significantly (3.9–13.4%). The location with the highest prevalence was an inner city residential site where positive mice were found significantly clustered within blocks and households. In this location, LCMV antibody prevalence was also significantly correlated with estimates of mouse density within individual blocks. The focal nature of LCMV infection in house mice may result from contact or vertical transmission of virus in conjunction with the highly structured social system of mice, which promotes inbreeding and limited dispersal.