GFP- and luciferase2-expressing MSCs were injected in mice via V.jugularis or A.carotis. After five minutes blood was collected through a catheter, lysed and analyzed by flow cytometry. At 24h after cell infusion, blood was collected, mice were perfused with PBS, and organs (lungs, liver, kidneys, spleen, brain, heart) were isolated and investigated by bioluminescence imaging. Intravenously infused MSCs were only detected in the lungs 24h after infusion. At this time point no MSCs were detected in the blood and in other organs. Also intravenous infusion of freshly isolated bone marrow cells resulted in a GFP signal only in the lungs, but considerably less compared to GFP-MSCs. Arterially infused MSCs resulted in death of the animals shortly after cell infusion most likely by pulmonary embolism, since the only detected GFP signal occurred in the lungs and the level of circulating GFP-positive cells in the blood was below the detection limit of flow cytometry. Although MSCs are slightly larger than leukocytes, it appears that these cells are trapped specifically in the lungs, since they are able to pass the capillary bed of the systemic circulation. It needs to be clarified if this is due to the size of the cells or to size the pulmonary capillaries or specific receptor interactions. This may have important clinical implications of the therapeutically interesting MSCs, since the cells may be released from the lungs later thereby shifting the therapeutic window. It may also be envisaged to alter the properties of the MSCs by different culture conditions.