Hepatic fibrosis is a common feature of many chronic liver diseases. Given the ethical considerations of studies with humans and the limited availability of liver biopsies, there is a need for in vitro models to understand the molecular events involved in hepatic fibrosis. The aim of this work was to compare the behavior of two hepatic cell types involved in fibrogenesis: a liver stellate cell line (CFSC-2G) and primary hepatocytes, both in single and mixed cultures. Cell proliferation was measured as DNA synthesis, protein content, and cell cycle study; functionality as adenylate charge, metabolic rate, and albumin content; and extracellular matrix production as type I collagen content, total collagen synthesis/degradation, metalloproteinase-13 content, and interstitial collagenase activity. Protein content and DNA synthesis were higher in CFSC-2G than in cocultures. Adenylate charge, metabolic rate, and albumin content were impaired in cocultures. Type I collagen content and total collagen synthesis were similar in CFSC-2G and cocultures. Metalloproteinase-13 content was higher in CFSC-2G and cocultures compared with hepatocytes, whereas collagenase activity was only detectable in cocultures. These results suggest that the presence of hepatocytes in the cocultures affects negatively the cell proliferation, functionality, and extracellular matrix production. Cocultures of activated CFSC-2G and healthy hepatocytes are a useful model to study fibrogenesis in vitro since various functional alterations found in this pathology are reproduced.