Activated cell-mediated immunity is known to be accompanied by elevated concentrations of 7,8-dihydroneopterin which in high concentrations was found to interfere with the oxidant-antioxidant balance. In this study we investigated whether 7,8-dihydroneopterin mediates apoptosis of Jurkat T-lymphocytes via a CrmA- or Bcl-2-sensitive pathway. Transient transfection assays with CrmA and Bcl-2 expression constructs showed that apoptosis was not affected by CrmA whereas it was significantly decreased upon cotransfection with Bcl-2 constructs. Results suggest that 7,8-dihydroneopterin-induced apoptosis of T-lymphocytes is mediated by a Bcl-2-sensitive pathway.