L-Arginine plays an important role in protecting animals against ammonia intoxication, enhances immune function, stimulates wound healing, and is the precursor for the endothelium-derived relaxing factor, recently recognized as nitric oxide (NO). In this study, we investigated the influence of hepatic reperfusion on amino acid metabolism after human OLT. After 10 sec of reperfusion, the arterial plasma levels of L-arginine dropped from 105 +/- 12 mumol/L to 3.8 +/- 0.6 mumol/L (P < 0.001), whereas plasma ornithine increased from 40 +/- 5.5 mumol/L to 129 +/- 15 mumol/L (P < 0.001). The reduced L-arginine levels remained subnormal for several hours after OLT. This drop in plasma L-arginine was due to an arginase release from the implanted graft. Immediately after reperfusion, the plasma concentrations of arginase increased from pretransplantation values of 18 +/- 13 IU/L to 2384 +/- 1456 IU/L (P < 0.01). Measurement of plasma nitrite (NO2-) and nitrate (NO3-), which are the stable end products of NO, revealed that NO2- decreased about 50% after reperfusion (from 1.64 +/- 0.32 mumol/L to 0.80 +/- 0.17 mumol/L; P < 0.001), whereas NO3- levels remained unchanged (76 +/- 23 mumol/L vs. 63 +/- 8 mumol/L). We conclude that hepatic reperfusion causes L-arginine deficiency by liberating high amounts of arginase from the implanted graft. This L-arginine depletion may influence the NO synthesis in patients after OLT.