Many developmental and psychiatric disorders exhibit strong sex differences with males being biased towards diagnosis of developmental disorders. Interestingly, many of these disorders have been linked to early-life immune activation. One theory regarding increased male susceptibility involves the activation of immune factors in early life; however factors such as sex and microglia function affecting immune activation are not well understood. Microglia are the resident immune cells of the brain and respond to infections with rapid increases in cytokine release. We recently discovered that males have significantly more microglia in the hippocampus and amygdala compared to females on postnatal (P) day 4. Subsequently, we examined proinflammatory cytokine responses to neonatal infection at P4 in males and females 8 and 24 hours following a low dose of Escherichia coli (E.coli). Contrary to our predictions, males and females showed similar neuroimmune responses at P4 in the hippocampus, cerebellum, amygdala, and prefrontal cortex with neonatally infected animals showing exaggerated cytokine levels compared to saline controls ( p ′ s .05); however; in the periphery males showed significantly greater levels of IL-1Beta and TNF-alpha 8 hours following neonatal infection compared to females ( p ′ s .05). We are currently examining microglia response to an ex vivo immune challenge to address whether microglia may be inherently more reactive in a sex-dependent manner outside of cell number or peripheral immune signals.