Primary monolayer cultures of hepatocytes from the adult rat, mouse, frog, or other species are readily prepared, and simple incubation conditions (plastic or glass substrata, serum-free media) suffice for supporting cell viability. However, these fail to support individual functions of the hepatocyte uniformly at levels exhibited by the intact liver, and examples of striking culture-adaptive changes have been reported, some as early as 12 hours after cell plating. Of particular interest at present is the role of organic substrata in maintaining culture the phenotype of normal hepatic parenchymal cells. Collagen and other putative components of the intercellular matrix from normal liver have been examined in this regard, and work has now been extended to studies of the elaboration of matrix proteins by specific hepatic cell types. The findings are relevant both to the problem of maintaining differentiated cultures and to an understanding of pathologic states in vivo (e.g., fibrosis) that involve disturbances in matrix metabolism.