In different strains of inbred Syrian golden hamsters (Mesocricetus auratus), the lymphocytic choriomeningitis virus (LCMV) strains WE and Armstrong (ARM) produced systemic infection with infective virus and viral antigens detected predominantly in reticuloendothelial organs. Host and virus strain-dependent fatal wasting disease also occurred. After infection with WE, all MHA and PD4 hamsters died of a progressive wasting disease and infectivity persisted in organs at relatively high titres. LSH and CB strain hamsters resisted lethal disease and totally eliminated infection. LVG and LHC strain hamsters were intermediate in susceptibility to WE; some died of wasting and had persistently infected organs, while others cleared infection and survived. ARM was avirulent causing an inapparent infection in all hamsters. LCMV antibody responses were temporally comparable for all hamsters with either lethal or non-lethal infection. Histologically, lymphoid hyperplasia and low-grade systemic perivascular mononuclear leukocyte infiltration were found in all LCMV-infected hamsters. However, non-necrotic segmental ileal changes, which included vascular congestion, minimal haemorrhage and crypt epithelial growth extension into the intestinal wall, were found in susceptible hamsters when infected with the lethal WE strain.