The aim of the Multicentric Liver Transplant Spanish Study was to evaluate tacrolimus therapy at the reduced, initial oral dose of 0.1 mg/kg per day to maintain the immunosuppressive potency of the drug and to avoid toxicity. The dosage of tacrolimus (D), the trough blood concentrations (C), and the evolution of the ratio (D/C) were followed up for 2 years after transplantation in 50 adult patients (38 men, 12 women) undergoing liver allograft transplantation. A total of 1732 samples were analyzed using the IMx tacrolimus method. The overall mean+/-SD concentrations were 10.84 ng/ml+/-5.32 ng/ml. During the first month, the median of the tacrolimus levels was 8.40 ng/ml, and 73.1% of the analyzed samples were within the established therapeutic range. The median oral tacrolimus dose was progressively reduced from 0.12 mg/kg per day during the first month to 0.058 mg/kg per day at the end of study period. A significant negative association was observed between the ratio of D/C and the post-transplantation period (r=-0.3624; p < 0.001). The median D/C ratio ranged from 0.0144 at the end of the first month to 0.0053 at 1 year. Significant declines in D/C were observed after the first and the third months after transplantation. The decrease in corticosteroid doses and the increase in serum albumin may explain the reduction in clearance with time.