Previous studies have demonstrated that treatment with 17β-estradiol (E 2 ) improves both spatial and nonspatial memory in young female mice. Still unclear, however, are the molecular mechanisms underlying the beneficial effects of E 2 on memory. We have previously demonstrated that a single post-training intraperitoneal (i.p.) injection of 0.2 mg/kg E 2 can enhance hippocampal-dependent spatial and object memory consolidation (e.g., Gresack and Frick, 2006b). Therefore, in the present study, we performed a microarray analysis on the dorsal hippocampi of 4 month-old female mice injected i.p. with vehicle or 0.2 mg/kg E 2 . Genes were considered differentially expressed following E 2 treatment if they showed a greater than two-fold change in RNA expression levels compared to controls. Overall, out of a total of approximately 25,000 genes represented on the array, 204 genes showed altered mRNA expression levels upon E 2 treatment, with 111 up-regulated and 93 downregulated. Of these, 17 of the up-regulated and 6 of the down-regulated genes are known to be involved in learning and memory. mRNA expression changes in 5 of the genes were confirmed by real-time quantitative PCR analysis, and protein changes in these same genes were confirmed by Western blot analysis: Hsp70, a heat shock protein known to be estrogen responsive; Igfbp2, an IGF-I binding protein; Actn4, an actin binding protein involved in protein trafficking; Tubb2a, the major component of microtubules; and Snap25, a synaptosome-specific protein required for neurotransmitter release. The types of genes altered indicate that E 2 may induce changes in the structural mechanics of cells within the dorsal hippocampus that could be conducive to promoting memory consolidation.