We hypothesised that T(reg) cells preferentially expand/infiltrate inside murine mesotheliomas. Immunotherapy based on the manipulation of T(reg) cell populations should therefore be targeted to the tumour site. The AE17 murine mesothelioma model was used for this study. Both intra-tumoural T(reg) cells and those in the periphery of tumour-bearing mice were identified by flow cytometry. The effect on tumour growth of intra-tumoural depletion of T(reg) cells using the PC61 anti-CD25 mAb was then examined. We identified CD4+ T(reg) cells co-expressing both the CD25 cell surface marker and the transcription factor Foxp3 within murine mesotheliomas. These intra-tumoural T(reg) cells increase significantly as a percentage of total CD4+ T cells within the tumour as it grows. We showed that the depletion of intra-tumoural T(reg) cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of T(reg) cells is a new, clinically relevant treatment option for established tumours.