We sought to determine whether pretreatment serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis C virus (HCV) correlate with demographic features and other disease characteristics and whether these values influence response to therapy. A total of 1,744 patients with HCV received either interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT determinations at entry visit of ≤1.3 × the upper limit of normal (ULN). By analysis of variance both pretreatment histologic activity index (HAI) scores (P < .0001) and fibrosis scores (P = .003) were significantly lower among patients with baseline ALT levels ≤1.3 × ULN. Individuals with lower pretreatment ALT values were younger and weighed less than the ALT >1.3 × ULN cohort. Baseline ALT was not related to gender, race, baseline viral level, or HCV genotype. Using logistic regression analysis, the only demographic feature associated with ALT ≤1.3 × ULN was lower baseline weight and lower baseline HAI score. There was no difference in sustained response between patients with baseline ALT levels ≤1.3 × ULN and those with >1.3 × ULN, in all treatment groups (26 of 105, 24.8% for ALT ≤1.3 × ULN; 440 of 1,639, 26.8% for ALT >1.3 × ULN). We conclude that HCV patients with minimally raised ALT values (≤1.3 × ULN) weigh less, and have lower histologic inflammatory scores than patients with more conventionally elevated ALT levels. Despite these differences, these patients have a similar sustained response to antiviral therapy.