Environmental enrichment may protect against some of the adverse behavioural and biological effects of stressors. However, unlike the effects seen in some species, among male mice housed in groups, enrichment may alter social stability, encourage competition and aggression, and thus promote the establishment of a stressful environment. A potent psychosocial stressor such as social defeat in mice promotes brain neurochemical changes as well as pro-inflammatory cytokine variations in the prefrontal cortex (PFC) and hippocampus. The present investigation demonstrated that enrichment in group-housed male mice, even in the relatively nonaggressive, although highly anxious BALB/cByJ strain encouraged the effects of a repeated social defeat stressor experienced 4weeks later, especially with respect to corticosterone as well as hippocampal corticotropin-releasing hormone (CRH) and interleukin (IL)-6 variations. Moreover, within the hippocampus, enrichment itself was accompanied by modest reductions in the expression of the IL-1β receptor (IL-1r1). Thus, it seems that living in an enriched environment among group-housed male mice might promote a stressful environment that enhances basal hippocampal CRH and cytokine variations and increased vulnerability to further changes upon subsequent exposure to a social stressor.