A novel model depicting a dynamic balance between sex chromosome complement and circulating testosterone on anxiety (black dotted line). A conventional interpretation in the sex difference field is that XY sex chromosome complement may exert a compensatory effect to reduce differences otherwise induced by circulating testosterone or vice versa. Data outlined in this review suggests that this is also the case for the regulation of mood and anxiety-like behaviors. Specifically, while male sex chromosome complement causes an increase in anxiety-like behavior, this effect is opposed by testosterone’s antianxiety effect. While sex chromosome complement appears to be acting via control of gene expression, we hypothesize that testosterone affects the activity of certain inhibitory GABA cell types (e.g., SST cells).