Objective methods are needed to quantitatively assess the burden of fibrous tissue in liver biopsy specimens and its changes after treatment. The aim of this study was to assess the validity of a computer-assisted morphometric method in the evaluation of liver fibrosis in patients with chronic hepatitis C. Sixty-nine liver biopsy specimens stained with Sirius red were evaluated by two independent observers with a computer-assisted morphometric method to measure the percentage of fibrous tissue in the optic fields examined (fibrosis ratio). Furthermore, 11 pairs of liver biopsy specimens obtained before and after treatment from patients with chronic hepatitis C were evaluated with morphometry by two independent observers in order to assess in which direction fibrosis changed. In the 69 patients, the correlation of the morphometry-measured fibrosis ratio pairs by the two observers was high (r = 0.781). However, the differences between paired values were large, reaching +/- 5% in 95% of instances. The fibrosis ratios observed with morphometry by the two examiners correlated poorly with the Ishak's staging score. The two examiners agreed in 10 out of 11 instances in judging in which direction fibrosis had changed. In conclusion, using our present technique of computer-assisted morphometry, the quantitative assessment of the percentage extension of fibrous tissue was not sufficiently accurate. However, computer-assisted morphometry proved to be useful when evaluating the direction of fibrous changes in pairs of liver biopsy specimens from patients with chronic hepatitis C before and after treatment.