FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity had higher FK506 whole-blood and plasma levels (27.5±3.2 ng/ml and 1.44±0.14 ng/ml) than patients with stable liver function (15.2±2.1 ng/ml and 0.98± 0.15 ng/ml, P<0.05 and P<0.01, respectively). Patients with acute rejection had FK506 whole-blood and plasma levels within the same range as patients with stable liver function. Patients with severe neurotoxic-ity had significantly higher FK506 whole-blood and plasma levels (31.3±6.8 ng/ml and 3.9±1.4 ng/ml) in comparison with patients with mild-to-moderate neurotoxicity (18.1±2.4 ng/ml and l.l±0.13 ng/ml) (P=0.048 and P<0.001, respectively). Long-term use of FK506 was associated with a significant reduction in glomerular filtration rate at 1-year posttransplant in patients on primary FK506 treatment (33%, P<0.001).