Donor-specific immunosuppression is important in transplant surgery. We examined the effect of intraportal donor-specific bone marrow transplantation on heterotopic small bowel transplantation in the high responder rat combination, ACI to Lewis. The study comprised five treatment groups: untreated controls (group 1); FK506 alone (group 2); low-dose predonine + FK506 (group 3); high-dose predonine + FK506 (group 4); and intraportal donor-specific bone marrow transplantation + FK506 (group 5). Intraportal transplantation was performed pre-operatively and FK506 and predonine given post-operatively. Intestinal allograft survival and changes of intragraft cytokine expression were analysed using the reverse transcription polymerase chain reaction. Allograft survival (mean +/- SD) was lowest in group 1 and greatest in group 5. The group 5 treatment regimen also down-regulated interferon-gamma and interleukin-2 transcription in the transplanted intestine. Intraportal donor bone marrow transplant combined with FK506 immunosuppression was found therefore to be the most beneficial treatment regimen.