Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 +/- 19.0 to 63.9 +/- 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 +/- 537 to 906 +/- 377 dyn s/cm(5) (p = 0.047). CO increased from 3.39 +/- 0.79 to 3.85 +/- 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 +/- 82 to 399 +/- 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.