Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, nϭ18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (⌽ 1 and ⌽ 2 ). SI of donors declined by day 10 after operation (SI 2.65 Ϯ 0.41 vs. 4.90 Ϯ 0.50 10 Ϫ4 minute Ϫ1 U ml Ϫ1 , P Ͻ 0.01) but returned to values as before after 6 months. ⌽ 1 did not change. ⌽ 2 , however, significantly increased by day 10 (8.57 Ϯ 0.82 10 9 minute Ϫ1 to 13.77 Ϯ 1.53 10 9 minute Ϫ1 , P Ͻ 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. ⌽ 1 did not alter in recipients. ⌽ 2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, ⌽ 1 and ⌽ 2 was detected.