AbstractEpigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic–pituitary–adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, includingn= 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1_D, 1_F, and 1_Hof the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1_Dand 1_Fin the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.