Mice infected with Schistosoma mansoni represent a model for study of the most prevalent form of hepatic fibrosis in humans. In the present study, collagenase activity was measured in relation to collagen synthesis and accumulation in the livers of mice 6-11 wk after after infection. Total and latent collagenase and elastase activities and collagen synthesis were maximal 8 wk after infection and decreased thereafter, whereas collagen content progressively increased to the 11th wk. Maximal enzymatic activity coincided with the known peak of host cellular immune responses. Collagenase and elastase activities were isolated from liver homogenates. Isolated schistosome eggs did not contain collagenase or elastase activities. Collagenolytic activity had the characteristics of a tissue collagenase. These data show that marked increases in collagenase activity occur together with increased collagen synthesis in this animal model. Continued accumulation of liver collagen under these conditions suggests an imbalance between increased collagen synthesis and degradation.