The IL-2 gene expression is highly T-cell specific in an activation-dependent manner. However, little is known about how T-cell specific expression is regulated, although related transcription factors have been identified. To address this issue, we examined the chromatin structure change of the IL-2 gene by analyzing histone acetylation status in the upstream of IL-2 gene transcription initiation site. Interestingly, the histone acetylation level was found to be higher in various sites on the widespread upstream region in resting T-cells than resting B-cells. After T-cell Stimulation with PMA and ionomycin, the same regions were further acetylated on histone H3. Particularly, the distal enhancer region showed prompt enhancement or histone acetylation, followed by the IL-2 mRNA expression. These results suggest that the 5' flanking region including the distal enhancer region of the IL-2 gene is already accessible in T cells with constitutive acetylation of histone H3,which may serve for T-cell specific IL-2 expression. © 2005 Elsevier Inc. All rights reserved.