The 5‐HT1Areceptor has been implicated in the modulation of anxiety processes, mainly via pharmacological experiments. The recent production, in three independent research groups, of 5‐HT1Areceptor knockout (R KO) mice in three different genetic backgrounds (C57BL/6J, 129/Sv, Swiss–Webster) led to the intriguing finding that all mice, independent from the genetic background strain from which the null mutants were made, showed an ‘anxious’ phenotype compared to corresponding wild‐type mice. The present paper reviews the behavioral findings in these three KO lines and focuses on new findings in the 129/Sv‐KO mice. These mice were more anxious or stress‐prone only under specific conditions (high stress) and not as broadly as suggested from the initial studies. The 5‐HT1AR KO made in the Swiss–Webster background displays disturbances in the GABAA–benzodiazepine (BZ) receptor system in the brain, including downregulation of GABAAα1and α2subunits in the amygdala. In contrast, the GABAA‐BZ receptor system seems to function normally in the 5‐HT1AR KO in the 129/Sv background suggesting that changes in the GABAA‐BZ receptor system may not be a prerequisite for anxiety but rather could have a modifying effect on this phenotype. It can be concluded that the constitutive absence of the 5‐HT1Areceptor gene and receptor leads to a more ‘anxious’ mouse, dependent on the stress level but independent from the strain. Depending on the genetic background, this null mutation may be associated with changes in GABAA‐ergic neurotransmission. It is as yet unclear which mechanisms are involved in this intriguing differentiation.