The influence of development and ethinylestradiol (EE) on apolipoprotein (apo) A-I, A-II, and E mRNA in rat liver and intestine was studied by dot blot hybridization and Northern blot analysis. ApoA-I mRNA levels were maximal in the perinatal period and declined after day 15. An opposite trend was noted for the apoA-II mRNA levels, whereas apoE mRNA remained fairly constant. Liver apoA-I mRNA levels increased after ovariectomy (OVX). A further rise was observed when EE was given at 2000 micrograms/day. When the influence of OVX and EE was controlled for food intake by pair-feeding, OVX still increased hepatic apoA-I mRNA. The rise in liver apoA-I mRNA after EE, however, was no longer significant. Under the same conditions OVX slightly increased intestinal apoA-I mRNA. EE (2000 micrograms/day) decreased intestinal apoA-I mRNA to 80% of the pair-fed controls. Liver apoA-II mRNA levels did not change after OVX when the animals were fed ad libitum, but decreased slightly when the rats were pair-fed. EE caused a dose-dependent decrease in liver apoA-II mRNA, irrespective of food intake. None of these treatments caused any change in liver apoE mRNA levels. Serum apoA-I levels increased upon OVX, while serum apoE did not change. EE provoked a dose-dependent decrease of both apolipoproteins in serum. In conclusion: 1) Changes in food intake play an important role in the in vivo effects of estrogens on apolipoprotein mRNA levels. 2) The stimulatory effect of OVX on hepatic apoA-I mRNA as well as the inhibitory effect of EE on hepatic apoA-II mRNA are independent of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)