DPP IV is a cell surface ectoenzyme widely distributed in the human body. It has been implicated in T-cell activation, hepatocyte-extracellular-matrix interactions and fibroblast proliferation. Furthermore, upregulated CD26 expression has been found on the surface of human hepatoma cells transfected with hepatitis C virus (HCV) c-DNA. We examined the serum DPP IV activity in a large number of patients with chronic HCV infection in a cross-sectional study. We also investigated whether the activity differs from that in controls and depends upon the response to interferon (IFN) therapy. Serum DPP IV activity was measured by microplate-based (Multiskan-Plus-MKII, Labsystem) kinetic assay in 144 patients with chronic HCV infection. Seventy-four out of 144 patients (46 nonresponders, 28 responders) were formerly treated with interferon. Sixty healthy blood donors served as controls. Gly-Pro-PNA (Bachem, Torrance, USA) was used as substrate. Results are expressed in nmol/ml/min (U/l). Shapiro-Wilk's test, Mann-Whitney U test and Spearman rank order correlation were used for statistical analysis. Serum DPP IV activity was significantly higher (mean = 20.89 [s 9.6]) in patients with chronic HCV infection than in healthy controls (12.39 [2.76, P < 10^-5]). The enzyme activities significantly differed in naive HCV-positive patients (22.2 [9.89, P < 10^-5]) and nonresponders (23.28 [9.57, P < 10^-5]) from that in the healthy controls and also from that in responders (13.69 [4.21]). Correlation was found between DPP IV activity and AST (r = 0.44, P < 10^-5), ALT (r = 0.44, P < 10^-5), GGT (r = 0.41, P < 10^-5) levels. Serum DPP IV activity seems to be an indicator of HCV induced liver injury. The activity may reflect the efficacy of interferon therapy.