The novel nociceptin/orphanin FQ (N/OFQ) system was proposed to be an important component of neural circuits involved in stress-coping behaviour and fear. This study investigated whether variations between the mouse strains in vulnerability to social crowding stress might be linked to different regulation of N/OFQ system transcripts in mice. Three weeks old C57BL/6J (B6), BALB/cByJ (CBy) and 129S2/SvPas (129S2) male mice were housed individually or in crowded (7/cage) conditions and then tested as adults in a battery of anxiety tests (open field, elevated plus-maze and acoustic startle reflex tests). Both 129S2 and B6 mice displayed increased signs of anxiety under crowded housing, while CBy mice tended to show the opposite profile. Analysis of gene expression revealed a 10-fold increase of nociceptin precursor and 4-fold increase of the NOP receptor mRNAs contents in the hippocampus of CBy mice kept in crowded conditions compared to those housed individually. In B6 mice, mRNA level of the peptide precursor remained unchanged, while that of the receptor was increased by 2-fold under crowding compared to individual housing. No significant changes were detected in 129S2 mice. These findings show that social housing may be important environmental stress factor in mice depending on the strain. The possible involvement of central nociceptin mechanisms in behavioural resilience to social crowding stress is discussed.