The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271⁺ MSCs in human peripheral blood and investigate whether the cells are mobilized after acute myocardial infarction (MI). A flow cytometric analysis identified CD45^low/−CD34⁺CD271⁺ cells in adult human peripheral blood. The numbers of circulating CD45^low/−CD34⁺CD133⁺ cells (hematopoietic linage progenitors) were significantly lower in elderly subjects without coronary artery disease than in healthy young subjects, whereas the numbers of CD45^low/−CD34⁺CD271⁺ cells were comparable between elderly subjects and younger subjects. The CD45^low/−CD34⁺CD271⁺ and CD133⁺ cell counts were both higher in patients with acute MI than in patients with stable coronary artery disease. In our investigation of the time course changes after acute MI, the CD45^low/−CD34⁺CD133⁺ cell counts gradually increased up to day 7. Over the same period, the CD45^low/−CD34⁺CD271⁺ cell counts peaked at day 3 and then declined up to day 7. Importantly, the CD271⁺ cell counts at day 3 were positively correlated with the peak concentrations of creatine kinase after acute MI. Results of the present study suggest that the CD271⁺ MSCs are mobilized differently from the CD133⁺ hematopoietic progenitors and may play a specific role in the tissue repair process during age-related changes and after acute myocardial infarction.