Regulatory T cells migrate into allografts and induce tolerance of the graft. Immunosuppressive regulatory T cells (Treg) are found among CD4⁺CD25⁺⁺ T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesised that activated T cells (TC) and Treg might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated TC and CD4⁺CD25⁺⁺Treg, in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients (n=22) compared to controls (n=18). Systemic levels of circulating Treg were significantly lower in CA recipients (8.9±1.3/ul) compared to controls (15.8±1.6/µl; p=0.002). Similarly, the proportion of Treg related to the total leukocyte number was significantly lower in CA recipients (p<0.01). In contrast, systemic levels of circulating activated CD4⁺ TC and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of Treg significantly decreased during transcardiac passage (3.0±0.3 to 2.4±0.3 % of CD4⁺ T cells, p<0.01), and FOXP3⁺ TC invaded into the allograft. In contrast, numbers of activated CD4⁺ TC increased during passage through the allograft even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive Treg are reduced in transplant recipients. Recruitment of Treg into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.