Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis (kappa = 0.59) than for activity (kappa = 0.43) and poor for lobular necrosis (kappa = 0.15). The mean agreement was better for senior (0.60 +/- 0.24) than junior pathologists (0.52 +/- 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 +/- 0.18 vs. 0.58 +/- 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: kappa = 0.48 and 0.77, activity: kappa = 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity (kappa = 0.22-0.25) or fibrosis (kappa = 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading.