We have recently reported that intake of soya protein isolate (SPI) inhibited the DNA-binding activities of hepatic thyroid hormone receptor (TR). The genes for acetyl-CoA carboxylase (ACC), a rate-limiting enzyme in fatty acid synthesis, contain the thyroid hormone response element in their promoters and are regulated by TR. The present study has examined the effect oflong-term feeding of SPI and soya isoflavones (ISF) on the gene expression and protein phosphorylation of different ACC isoforms in different tissues and plasma triacylglycerol (TAG) levels in rats. Sprague-Dawley female rats were fed diets containing 20% casein or alcohol-washed SPI with or without supplemental ISF for 70, 190 and 310d. SPI intake significantly reduced plasma TAG concentrations compared with casein, whereas supplemental ISF had no effect. Hepatic ACCα and ACCβ mRNA abundance and protein content were markedly lowerin the rats fed SPI than in those fed casein. The protein contents of ACCα in the kidneyand ACCβ, the predominant isoform in the heart and kidney, were unchanged by dietary SPI.The ratios of phospho-ACCα/ACCα and phospho-ACCβ/ACCβ were not differentamong dietary groups in all tissues measured. The present study demonstrates that ingestion ofSPI decreases plasma TAG level and down-regulates ACCα and ACCβ gene expression in the liver but not in the heart and kidney. The results indicate that the effect of SPI is tissue-specific and that alteration of ACC gene expression rather than phosphorylation status may play a major role in the regulation of ACC activities by soya proteins.