Treatment of male rats with hydrocortisone provoked a dose- and time-dependent decrease in plasma cholesterol concentration without a change in plasma triglyceride levels. In contrast, administration of triamcinolone and dexamethasone at equipotent glucocorticoid doses increased plasma cholesterol and triglyceride levels, respectively. Small effects on apolipoprotein E (apo E) and apo B mRNA levels were observed, but all corticosteroids increased apo A-I and apo A-IV mRNA and decreased apo A-II mRNA levels in the liver. Triamcinolone and dexamethasone, however, were three times more potent in stimulating hepatic apo A-IV gene expression than was hydrocortisone, whereas liver apo A-I and apo A-II mRNA levels were altered to a similar extent by all corticosteroids. Plasma apo A-I and apo B concentrations always varied in a similar fashion with their respective liver mRNA levels after administration of the distinct corticoids. For apo A-IV and apo E, discrepancies between plasma and liver mRNA levels after administration of the different steroids, however, point to additional regulatory effects on plasma apolipoprotein levels. We conclude that 1) in contrast to plasma apo A-I and apo B, alterations in plasma lipid, apo A-IV, and apo E levels depend on the type of corticosteroid used; and 2) glucocorticoids have a differential effect on hepatic mRNA levels of apo A-I and apo A-IV on the one hand and apo A-II on the other hand, an effect that may be of consequence in the process of reverse cholesterol transport.