The aim of the present study was to assess whether EPC (endothelial progenitor cell) number/function might be an explanatory factor for the observed relationship between Type D personality (a joint tendency towards negative affectivity and social inhibition) and poor cardiovascular prognosis. We also assessed whether the effect of a single exercise bout on EPC number/function was affected by Type D personality. A total of 35 sedentary men with CHF (chronic heart failure; left ventricular ejection fraction <or=45%) underwent CPET (cardiopulmonary exercise testing) and personality assessment with the 14-item Type D scale. CD34+/KDR (kinase insert domain-containing receptor)+ cells were quantified by flow cytometry before and immediately after CPET. Migration of early EPC towards VEGF (vascular endothelial growth factor) and SDF-1alpha (stromal-cell-derived factor-1alpha) was investigated. Type D (n=10) and non-Type D (n=25) patients were comparable with regards to demographics, disease severity and Framingham risk factor score. Circulating EPC numbers were reduced by 54% in Type D compared with non-Type D patients (0.084+/-0.055 and 0.183+/-0.029% of lymphocytes respectively; P=0.006). Exercise led to a 60% increase in EPC in Type D patients, whereas the EPC number remained unchanged in the non-Type D group (P=0.049). Baseline migratory capacity was related to disease severity, but was not different between Type D and non-Type D patients. Exercise induced a highly significant enhancement of migratory capacity in both groups. In conclusion, reduced EPC numbers might explain the impaired cardiovascular outcome in Type D patients. The larger increase in circulating EPCs observed in these patients suggests that acute exercise elicits a more pronounced stimulus for endothelial repair.