MHC class I and class II molecules are expressed in soluble form in the serum of both healthy and diseased individuals. Our aim was to investigate whether soluble class I (sHLA) levels in allograft patients correlate with their clinical status. Altogether, 20 renal and 30 cardiac graft recipients were examined. High levels of sHLA were measured at least 5 days preceding acute rejection episodes. Immune complexes between anti-HLA antibodies and sHLA were detected in a patient who died of a severe vascular rejection. In another study the interaction of papain-derived sHLA on alloreactive CTL in vitro was investigated. In a chromium-51-release cytotoxicity assay, 1.25 microg/ml of papain-digested class I molecules reduced CTL cytotoxicity to background levels. On the contrary, immobilized molecules triggered the release of serine esterase allospecifically. These data showed that the MHC molecule alone was a sufficient ligand for the interaction with alloreactive CTL.