Epigenetic factors translate environmental signals into stable outcomes, but how they are influenced by regulators of plasticity remain unclear . We previously showed that androgen receptor overexpression inhibited fear memory in male mice and increased expression of the histone variant H2A.Z, a novel epigenetic regulator of memory . Here, we used conditional-inducible H2A.Z knockout mice to investigate how H2A.Z deletion influences androgenic regulation of fear memory . We showed that conditional inducible H2A.Z deletion blocked memory-enhancing effects of androgen depletion (induced by gonadectomy), and of pharmacological inhibition of the androgen receptor with flutamide . Similarly, H2A.Z deletion blocked the memory-reducing effects of DHT, and DHT treatment in cultured hippocampal neurons altered H2A.Z binding, suggesting that AR is an H2A.Z regulator in neurons . Overall, these data show that fear memory formation is regulated by interactions between sex hormones and epigenetic factors, which has implications for sex differences in fear-related disorders.