We have reported that two types of ERs, ERa and ERb, are differentially involved in the estrogenic regulation of various kinds of social behaviors in both sexes of mice. In contrast to ERa-dependent action, the neuronal mechanisms of ERb action are still largely unknown. Using the ERb-RFPtg mouse line, we found a differential distribution of ERb from ERa at the “cellular level” in each of the ERb-rich brain regions in the social behavior neural network, such as the medial amygdala (MeA), lateral septum, and midbrain dorsal raphe nucleus (DRN). To further determine the functions of these ERb-expressing neurons in the neuronal network for social behavior, we have conducted a series of studies with the use of chemogenetic manipulation as well as fiber photometry recording in newly developed ERb-iCre mice. We have found that ERb-expressing neurons in the posterodorsal MeA (MeAPD) play a role in the establishment of sexual preference in male mice by affecting neuronal activity in the principal part of the bed nucleus of the stria terminalis. A separate line of investigation in female ERb-iCre mice revealed that ERb-expressing cells in the DRN may be involved in the inhibitory regulation of female sexual behavior induced by ERa-mediated estrogen action. These findings collectively suggest that ERb-expressing neurons in the social behavioral neural networks play a significant role in the adaptive expression of social behavior in both male and female mice. (Supported by 15H05724, 21K18547, and 22H02941 to SO.)