Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and is accompanied by systemic increases in CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Treg). To determine their effect on ischemic brain injury, Treg were depleted in Foxp3(DTR) mice prior to stroke induction. In contrast to a recent Nature Medicine report, our results demonstrate unequivocally that Treg depletion did not affect stroke infarct volume, thus failing to implicate this regulatory pathway in limiting stroke damage.