Human liver allografts deliver soluble class I (HLA-A and -B) transplantation antigens into the recipients' circulation. These molecules are detectable in recipient serum shortly after transplantation and they persist at high concentration for as long as the liver graft functions. Levels of graft-derived antigens in the recipient serum and self antigens in donor serum are comparable. Kinetic studies of these soluble antigens in donor and recipient show that donor antigens are continuously exported by the transplanted liver, while in the recipient, self antigens are derived from liver and other sources. At least two molecular forms of soluble HLA-A and -B antigens are present in sera from donors, recipients, and normal individuals. One form with m.w. approximately 50 kd seems to be a soluble monomer associated with beta 2-microglobulin, while the other forms of higher m.w. may be aggregates and/or complexes. Monitoring of these antigens in transplant recipients may be a useful indicator of graft pathology and function.