Abstract Peripheral blood T cells were isolated from 19 allogeneic and 4 autologous stem cell transplant (SCT) recipients and assessed for tumor necrosis factor (TNF)–α and interferon (IFN)–γ transcription by reverse transcription-polymerase chain reaction. Levels were compared with resting donor T-cell transcription levels. Increased production of TNF-α predicted for the onset of severe (grade II-IV) graft-versus-host disease (GVHD) ( P = .001). Increased TNF-α ( P = .025) and IFN-γ ( P = .001) transcription also independently predicted for the eventual onset of extensive chronic GVHD. Increased TNF-α or IFN-γ transcription was not seen in either a syngeneic SCT recipient or 4 autologous SCT controls. These findings provide a means by which GVHD can be predicted before it is clinically evident, thus allowing for accurate diagnosis and monitoring of GVHD and possibly more cost-effective management of post-SCT immunosuppression.