When rat hepatocytes were cultured in serum-free and hormone-free Waymouth's medium, secretion rates of apolipoproteins (apo) AI and AIV were stable for two days, while the secretion rate of apo E decreased only 20% on the second day. Effects of insulin and dexamethasone on hepatic secretion of apo AI, apo E, and apo AIV were studied in primary culture of rat liver cells within two days. Adding insulin alone and dexamethasone alone, 1 mumol/L each, to cultured hepatocytes for 20 hours had little effect on the amounts of apo AI secreted by the cells. But when the treatment with either insulin or dexamethasone was prolonged for 44 hours, apo AI secretion by treated cells was increased 2.0-fold and 1.4-fold over that by control cells, respectively. If both hormones were added together, secretion of apo AI was synergistically increased 1.5-fold and 7-fold after 20 and 44 hours incubation, respectively. The optimal concentrations of both hormones for the synergistic effect were 0.1 mumol/L. Insulin alone did not affect, while dexamethasone alone slightly suppressed, apo E secretion by hepatocytes. However, when hepatocytes had been incubated with both hormones, a 70% increase in the release of apo E into the culture medium was also observed after 20 hours. Insulin caused a two-fold increase in cellular apo E in hepatocytes. The insulin-mediated cellular accumulation of apo E could be enhanced only very slightly by dexamethasone, but was completely blocked by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)