The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 mug pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy of blocking virus production (epsilon) and infected cell loss during treatment (mdelta) compared with patients with elevated ALT levels. Differences were significant for epsilon (P = .02) and delta (P = .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters epsilon, delta, and mdelta was observed in patients with elevated gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.