This chapter reviews biological and genomic variability among arenaviruses and arenavirus-induced disease, especially in experimental laboratory infections. The source of virus was linked to persistently infected tumor cell lines and infected pet hamsters that had been obtained from a persistently infected breeding colony. E. Traub first described the phenomenon of persistent lymphocytic choriomeningitis virus (LCMV) infection in laboratory mice and the fundamental pathogenic consequences of acute virus infection. LCMV has been recognized as a manipulable and reproducible model for infection of laboratory mice, and several investigators have established independent virus isolates that have subsequently been passaged under different conditions. The isolation and characterization of reassortant viruses from unique parental LCMV strains has produced considerable new information. The frequency of recovery of reassortant viruses appears to have varied according to the pairing of parental LCMV strains. Experiments involving direct RNA sequencing of virion RNA preparations are in progress to examine the frequency of sequence change at the population level.