Background and Purpose-Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34ϩ stem cells. Methods-We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 g/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34ϩ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results-Thirty-six patients, whose meanϮSD age was 76Ϯ8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 g/kg) increased CD34ϩ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, Pϭ0.005). A dose-dependent rise in white cell count (PϽ0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions-G-CSF is effective at mobilizing bone marrow CD34ϩ stem cells in patients with recent ischemic stroke.Administration is feasible and appears to be safe and well tolerated.