Apolipoprotein A-I (apoA-I) gene expression is known to be regulated by nutritional and hormonal factors. Experiments were conducted to determine the effects of vitamin A deficiency and retinoic acid repletion on the in vivo expression of apoA-I in rat intestine and liver. The relative abundance of apoA-I mRNA (apoA-I/beta-actin ratio) in the intestine did not differ significantly between vitamin A-deficient and -sufficient rats. However, the relative abundance of hepatic apoA-I mRNA of vitamin A-deficient rats was 2.2- to 6-times that of sufficient rats. Even marginal vitamin A status resulted in a significant increase in hepatic apoA-I mRNA expression. Treatment of vitamin A-deficient rats with a single dose of retinoic acid (20 micrograms, 20 h before tissues were collected) reduced the hepatic apoA-I mRNA/beta-actin ratio by about 40%, while further reduction (about 60-65%) was observed after two treatments with retinoic acid. By nuclear run-on assay, the increase in hepatic apoA-I mRNA in vitamin A-deficient rats was attributable to increased transcription of the apoA-I gene. However, immunoblot analysis showed no apparent differences in apoA-I protein in either liver homogenates or plasma of vitamin A-deficient and -sufficient rats. These data indicate that apoA-I gene expression in vivo is sensitive to retinoid status and suggest that there is additional regulation of post-transcriptional events.