Estrogens exert important actions on fear and anxiety in both humans and non-humans. Currently, the mechanisms underlying estrogenic modulation of fear are not known. However, evidence suggests that estrogens may exert their influence on fear and anxiety within the amygdala. The purpose of the present study was to examine the genomic effects of estrogens within the amygdala of female mice using high-density oligonucleotide microarrays. We examined the effects of estrogens on gene expression at 2 and 24 h after an acute subcutaneous injection. Data from the microarrays revealed that 2 h following an acute injection of estradiol, 44 genes were significantly up- or downregulated, and at 24 h, 13 transcripts were significantly up- or downregulated. One interesting estrogen-regulated gene, (CaMKIIalpha), was downregulated ninefold 2 h following an acute estradiol injection but was not altered 24 h after injection. We further examined estrogen regulation of CaMKIIalpha, as well as CaMKIIbeta and CaMKIV within the amygdala using quantitative PCR and western blot analysis. The data indicate that estrogen decreases CaMKIIalpha and CaMKIV but not CaMKIIbeta gene expression within the amygdala. However, CaMKII protein levels were not different, and CaMKIV protein levels increased 2 h post-EB treatment. These results indicate that estrogen regulates CaMK gene expression and protein levels within the amygdala.