The behavioural phenotype of mice, lacking CCK(2) receptors, has varied across studies conducted not only in different laboratories, but also across studies published by the same laboratory. The present study was designed to elucidate the phenotype of CCK(2) receptor-deficient mice housed in two different environmental conditions within the same laboratory. Environmental enrichment was used as an alternative environment to standard laboratory conditions. Significant genotype by environment interaction was observed in the plus-maze, hot-plate, restraint-induced analgesia and water maze test. While mice, lacking CCK(2) receptors, housed in standard conditions were more anxious, displayed stronger restraint-induced analgesia and performed worse in the water maze when compared to corresponding wild-type littermates, none of these phenotypes were observed in mice, housed in enriched conditions. By contrast, in the hot-plate test, rota-rod and locomotor activity test a genotype-dependent phenotype was observed in mice housed in enriched, but not in standard conditions. Moreover, the phenotype of CCK(2) receptor-deficient mice established in the hot-plate test and rota-rod was sex-specific. These results suggest that thorough and labour-consuming study of mutation-induced behavioural phenotype is necessary not only in different genetic backgrounds but also the substantial variation of phenotype due to sex- and environment-related factors have to be explored.