Using (LEW) parent to (LEW×WKA)F1 combination, heterotopic total small bowel transplantation was performed in rats. We divided this GVHD model into four groups (group 1 ; control, group 2 ; Cyclosporine A (CyA) 5mg/㎏ 0-2 pod, group 3 ; CyA 5mg/㎏ 0-6 pod, group 4 ; anti-ASGM1 antibody 50μ1 twice). All rats in group 1 developed cutaneous GVHD on 8 or 9 pod, and developed systemic GVHD and died within 19 pod (Mean Survival Times (MST)＝17.5±1.5). All rats in group 2 developed cutaneous GVHD on 11-14 pod and died in 20-25 pod due to systemic GVHD (MST＝22.7±1.6). However, 3 of the 7 rats in group 3 and none of those in group 4 developed cutaneous GVHD and survival times were elongated (MST≧107.6±106.9, 52.5±41.9). We also evaluated the cytotoxic activity of recipient spleen cells against three strains of rat skin cells (LEW, WKA, (LEW×WKA)F1) and K-562 cell line on 7 pod. In group 1 and 2, cytotoxic activity was augmented, compared with that in normal F1 rat, against all target cells. However, in group 3 and 4, cytotoxic activity was attenuated, compared with that in group 1 and 2, and lower than in normal F1 rat. We considered that this cytotoxic activity was due to MHC non-restricted NK cells, because there were no differences in any kind of target cells. We concluded that the NK cell might play a great role in GVHD, especially for skin lesions.