5-HT(1A) receptors play a critical role in the pathophysiology of anxiety and depression as well as in the mode of action of anxiolytic and antidepressant drugs. Mice with a targeted inactivation of the 5HT(1A) receptor show a phenotype that is associated with a gender-modulated and gene/dose-dependent increase of anxiety-related and antidepressant-like behaviours. Since this behavioural phenotype was observed in animals in which the mutation was bred into mice of different genetic backgrounds, 5-HT(1A) receptor knockout mice represent a useful model system for advanced investigations of 5-HT(1A) genotype/phenotype interaction.