Recent studies suggest that the mammalian heart possesses some capacity for cardiac regeneration. This regenerative capacity is primarily documented postnatally and after myocardial infarction or pressure overload. Although the cell type that mediates endogenous regeneration is unclear, cardiac stem cells might be considered as potential candidates. To determine the number of c-kit + cardiac resident cells under conditions of pressure overload, we evaluated specimens derived from n = 8 patients with pressure overloaded single right ventricles in comparison to n = 4 explanted hearts from patients with dilated cardiomyopathy and n = 14 biopsies from children after heart transplantation. The age of the patients ranged from 16 days to 19 years. For quantification of cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and expressed as percent of the total nuclei. In specimens from patients with dilated cardiomyopathy, 0.13 ± 0.09% c-kit +/mast cell tryptase-/CD45- cells were detected. However, in specimens from patients with pressure overloaded single right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were significantly higher (0.41 ±0.24%, p < 0.05). Under conditions of pressure overload, the right ventricle shows an approximately three-fold increase in c-kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this increased number of c-kit+ cells is not sufficient to prevent the failing heart from congestive heart failure, understanding the mechanism that leads to an increase of presumably cardiac resident stem cells under conditions of pressure overload might help to develop new strategies to enhance endogenous repair.