Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 10(7) BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.