Genetic influences on lordosis, a mammalian social behavior, are amenable for study because of the relative simplicity of both stimuli and response. The neural circuit for lordosis involves a supraspinal loop, which is controlled by an estrogen- and progesterone-dependent signal from the medial hypothalamus and results in heightened sexual motivation. In turn, this involves elevated states of arousal, defined by increased sensory alertness, motor activity and emotional reactivity. Mice in which the gene encoding the alpha form of the estrogen receptor (ERalpha) has been knocked out show that ERalpha is crucial for lordosis behavior. Comparing ERalpha-, ERbeta- and double knockouts reveals that different patterns of sexual behaviors in mice require different patterns of ER activity. Understanding how hormonal and genetic effects on deep motivational and arousal processes contribute to their effects on specific sexual and aggressive behaviors pose significant challenges for mouse functional genomics.