Early-life stress during the postnatal period could precipitate long-lasting alterations in the functional properties underlying emotional expression in humans, but how the psychological stress of cross-fostering affects emotional behavior during adulthood in mice remains primarily unknown. The purpose of the present study was to examine the long-term effects of cross-fostering on the emotional behavior and cognitive functions of ICR offspring in adulthood. Cross-fostering was performed from postnatal day 7 for 3 weeks. Mice were divided into three groups: (1) biological group: pups born from ICR dams fostered by their original mothers; (2) in-foster group: pups born from ICR dams but adopted by other ICR dams and (3) cross-foster group: ICR pups adopted by C57 dams. ICR mice were subjected to behavioral experiments at the age of 8 weeks. Emotional behaviors in the cross-fostered mice were significantly altered in the open-field, elevated plus maze and forced swimming tests, as well as social interaction tests. However, the cross-fostered mice showed normal memory function in the Y-maze and novel object recognition tests. The contents of serotonin metabolisms were decreased in the prefrontal cortex and hippocampus indicated the deficit of serotoninergic neuronal function by cross-fostering. These findings suggested that the early-life stress of cross-fostering induced long-lasting emotional abnormalities, which might be possibly related to alterations of serotonin metabolisms. © 2008 Elsevier B.V. All rights reserved.