Severe graft-versus-host disease (GvHD) refractory to corticosteroids responds poorly to experimental treatment and is often fatal. Attempts have been made to 'rescue' such patients by transfusing autologous cells in order to ablate the lymphoid component of the graft or to introduce regulatory cells capable of suppressing the GvHD. Here, we report details of eight patients with severe grade III-IV acute GvHD (n=7) or extensive chronic GvHD (n=1) who after failing a median of four lines of treatment were then treated with either autologous or syngeneic nucleated cell transfusions. Patients received standard conditioning (n=3), low intensity (n=2) or no conditioning (n=3) before the rescue procedure. In four of the five patients who received some form of conditioning, mixed chimerism or complete recipient hematopoiesis was restored. The GvHD resolved in four patients, of whom one died subsequently of multiorgan failure and two died of leukemia; one is still alive. A fifth patient had transient improvement in GvHD, which recurred when the corticosteroids were reduced. Three patients obtained no benefit from the procedure. We conclude that 'rescue' by transfusion of autologous or syngeneic nucleated cells may be valuable to treat severe refractory GvHD; the best approach to conditioning remains to be defined.