We compared the findings in the wasting syndrome seen in [MRL lpr/lpr--> MRL +/+] chimeras with those of chronic graft versus host disease (GVHD) in [B10.D2-->BALB/c] chimeras. BALB/c mice were lethally irradiated and administered B10.D2 spleen and bone marrow cells. These mice are identical to MHC and Mls but differ as to genetic background. As a result of chronic GVHD, these [B10.D2-->BALB/c] chimeras showed hair loss, weight loss and atrophy of lymph nodes and spleen beginning 5 weeks after the transplantation. MRL lpr/lpr mice carry the lpr gene and spontaneously develop generalized lymph node swelling and lupus-like autoimmune disease, while congenic MRL +/+ mice lack the lpr gene. The [MRL lpr/lpr-->MRL +/+] chimeras showed wasting and the same symptoms as in [B10.D2-BALB/c] chimeras beginning 16 weeks after cell transfer. Skin biopsy from both chimeras showed very similar changes on HE staining and on immunoperoxidase staining for Ia and Thy-1. Our data suggest that very small differences in minor histocompatibility may induce GVHD which produces severe wasting with lethal consequences. Finally, we succeeded in transferring the wasting syndrome seen in the [MRL lpr/lpr--> MRL +/+] chimera to other MRL +/+ mice by transplanting spleen cells from the [MRL lpr/lpr-->MRL +/+] chimera to lethally irradiated MRL +/+ mice.