The objective of this study was to examine the importance of cellular aggregation for the maintenance of liver-specific functions in hepatocytes. We used two culture matrix systems (collagen sandwich and Matrigel) to examine the responsiveness of albumin secretory function in cultured rat hepatocytes under various seeding conditions. With high cell seeding, both culture systems elicited comparable levels of elevated function. Under conditions of sparse seeding, however, their responses were quite distinct : collagen sandwiched cells exhibited a significant deterioration in secretion, while Matrigel-cu Itu red cells retained their basal levels of function. This indicates that a critical degree of cell-cell interactions is essential for promoting function in the collagen sandwich, and in the Matrigel-cultured cells functions may be preserved by constitutive matrix-related phenomena, even in the absence of aggregation.