Primary hepatocyte cultures are ideal models in which to investigate regulation of lipoprotein synthesis and catabolism by the liver. Not only can one regulate the physiological and nutritional state of the donor animal, but one can also manipulate the culture milieu. A possible problem that arises in prolonged incubations is the accumulation of metabolites in the culture media, which may alter the function of the cells. Studies using more novel culturing techniques such as "perifusion" may resolve this technical problem. This review indicates that caution must be used in analyzing data based on studies employing heterologous sera; additionally, closer attention should be given to the role of lipoprotein subfractions in regulating lipoprotein metabolism. It is now known that lipoprotein classes are heterogeneous with respect to metabolic origin and lipid and apolipoprotein content, hence they may have diverse physiological roles in hepatic lipid metabolism.