BACKGROUND: A picornavirus (Ljunganvirus [LV]) has recently been associated with disease during pregnancy in its natural rodent reservoir and in humans. A study of laboratory mice infected under controlled conditions was therefore undertaken. METHODS: CD-1 female mice were infected gestational day two and subjected to varying regimes of stress. RESULTS: LV infection in combination with stress resulted in uterine resorptions, malformations, and neonatal death. A short delay in time to first pregnancy and births was observed in pairs infected in utero. CONCLUSIONS: LV is found in different species of native animals in both Europe and the United States and human epidemiological evidence connects LV and human reproduction, while the observations here indicate that LV is responsible for reproductive problems in a laboratory mouse model. The current findings suggest that the hypothesis that LV also causes disease in pregnant women and their offspring deserves further study.