The present experiments tested the hypothesis that one of the critical mechanisms underlying genetically defined aggressiveness involves brain serotonin 5-HT 1A receptors. 5-HT 1A receptor density, the receptor mRNA expression in brain structures, and functional correlates for 5-HT 1A receptors identified as 8-OH-DPAT-induced hypothermia and lower lip retraction (LLR) were studied in Norway rats bred for 59 generations for the lack of aggressiveness and for high affective aggressiveness with respect to man. Considerable differences between the highly aggressive and the nonaggressive rats were shown in all three traits. A significant decrease in B max of specific receptor binding of [ 3 H]8-OH-DPAT in the frontal cortex, hypothalamus, and amygdala and a reduction in 5-HT 1A receptor mRNA expression in the midbrain of aggressive rats were found. 5-HT 1A receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p.) produced a distinct hypothermic reaction in nonaggressive rats and did not affect significantly the body temperature in aggressive rats. Similar differences were revealed in 8-OH-DPAT-induced LLR: LLR was expressed much more in nonaggressive than in aggressive animals. Additionally, 8-OH-DPAT (0.5 mg/kg i.p.) treatment significantly attenuated the aggressive response to man. The results demonstrated an association of aggressiveness with reduced 5-HT 1A receptor expression and function, thereby providing support for the view favoring the idea that brain HT 1A receptor contributes to the genetically defined individual differences in aggressiveness.