Hepatic ischemia reperfusion injury as well as acute graft rejection (RE) after orthotopic liver transplantation (OLT) are associated with leukocyte invasion of the graft. Local synthesis of chemokines is a key reaction in the recruitment and activation of inflammatory leukocytes and consequent liver damage. In this paper we describe the role of monocyte chemoattractant protein (MCP)-1 (CCL2) in human OLT. We investigated the serum CC-chemokine levels for MCP-1 by specific ELISAs after OLT in 105 human liver allografts between September 1997 and January 2001. One hour after reperfusion we saw a significant (t test) increase of MCP-1 in peripheral blood (92.5 +/- 85.8 pg/mL to 774.2 +/- 319.6 pg/mL, 8.3-fold, P <.0001), hepatic venous blood (92.5 +/- 85.8 pg/mL to 866.7 +/- 376.1 pg/mL, 9.3-fold, P <.0001), and portal venous blood (92.5 +/- 85.8 pg/mL to 792.9 +/- 408.0 pg/mL, 8.5-fold, P < 0.0001) during hepatic ischemia reperfusion injury. An analysis of the correlation (Spearman's test, rs) between the expression of MCP-1 and the AST (rs 0.555, P <.025) and ALT (rs 0.852, P <.0001) showed a significant linear correlation. During RE a significant (t test) increase of MCP-1 (125.5 +/- 95.6 pg/mL to 188.5 +/- 124.6 pg/mL, 3.86-fold, P <.0001) was demonstrated. The successful treatment of the RE led again to a decline to lower base levels. Hepatic ischemia reperfusion syndrome as well as RE after OLT are characterized by typical patterns of CCL-2 overexpression. This finding proposes a new noninvasive, early diagnostic test after OLT.