A statistically significant relationship was seen between inheritance of high TGF-beta1- and angiotensinogen (AT)- producing genotypes and the development of progressive hepatic fibrosis. This association persisted after correcting for potential confounders. Patients who inherited neither of the profibrogenic genotypes had no or only minimal fibrosis. Knowledge of these polymorphisms may have prognostic significance in patients with chronic HCV and may direct more aggressive therapy towards those patients with an increased risk of disease progression. The documen-tation of a significant relationship between AT genotype and fibrosis raises the novel suggestion that angiotensin II may be another mediator of extracellular matrix production in the liver.