The co-administration of T cell-depleted (TCD) syngeneic marrow protects against the acute graft-versus-host disease (GVHD) mortality which follows the administration of allogeneic bone marrow and lymphocytes to lethally irradiated mice. We have previously hypothesized that natural suppressor (NS) cells, which are present in the spleens of radiation chimeras in the early weeks after bone marrow transplantation (BMT), might be responsible for this protective effect. This hypothesis was based on the observation that NS activity in the spleens of recipients of mixed marrow inocula is mediated predominantly by cells derived from the syngeneic marrow component. This observation, however, was made in recipients of mixed inocula in which both the allogeneic and the syngeneic marrow components had been TCD. Such an approach was taken in order to avoid administration of allogeneic T cells and the suppressive activity which might develop due to the GVH reaction itself. It was, however, of interest to examine the suppressive activity developing in recipients of non-TCD allogeneic marrow plus TCD syngeneic marrow, since the anti-GVHD effects of host-type putative suppressor cells might be clinically relevant. The results presented here demonstrate that non-T cell-mediated suppressive activity develops in the spleens of recipients of non-TCD allogeneic marrow, consistent with the activity of NS cells.(ABSTRACT TRUNCATED AT 250 WORDS)