The nature and influence of adhesive interactions of rat hepatocytes with components of the extracellular matrix has been studied in culture. Hepatocytes interact with different kinetics to substrata composed of collagen type IV, laminin or fibronectin and adopt significantly different morphologies. The receptors mediating these various responses appear to be specific, according to the matrix, and in the case of fibronectin are complex, implicating several components of the hepatocyte surface. Collagen type IV maintains a differentiated phenotype more efficiently than fibronectin or laminin as measured by the production of adult hepatocyte markers such as albumin and repression of α-foetoprotein synthesis. Formation of matrix components is also influenced by the substratum: synthesis and secretion of fibronectin or collagen type IV is down-regulated when cells are cultured on the homologous substratum. Hepatocytes cultured in vitro secrete components of the coagulation cascade and also mediate fibrinolysis on addition of exogenous plasmin. The results are discussed in relation to the normal phenotype of the mature hepatocyte in vivo.