Summary. The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (±SD) patient age was 44.0 ± 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage ≥2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82–19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97–0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000–1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.