Using a solid phase enzyme immunoassay (ELISA) with three different murine monoclonal antibodies (mAb) to HLA (human leukocyte antigens) framework determinants, circulating HLA were detected and quantitated both in normal individuals as well as liver allograft recipients. In normal individuals, the level of circulating HLA remained constant for several months of this study. The quantity of antigens present in the sera was not influenced by the collection procedures. During the immediate post-transplant period there was detectable donor HLA in the recipient's circulation; however, no correlation was noted between graft function and the large quantity of donor HLA present in the sera. Within 5 months after transplantation there was a gradual decrease in the amount of circulating HLA compared to the level seen in normal individuals. These shed donor antigens may play an active role in initiating the development of tolerance to the transplanted organ.