The effects of the thyroid hormone (T₃) on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were evaluated in a baby hamster kidney cell line, C100. The cells cultured in MEM were supplemented with 10% thyroid hormone-depleted fetal bovine serum (THDS-MEM) and had a 82.5% lower level of HMG-CoA reductase activity than the cells grown in a medium supplemented with fetal bovine serum (FBS-MEM). When T₃ was supplemented to THDS-MEM, the reduction of the reductase activity was blocked in a dose-dependent manner. In the cells grown in THDS-MEM containing T₃ at a concentration of 10^(-6) M, the level of HMG-CoA reductase activity was 91.8% relative to the cells grown in FBS-MEM. These changes in HMG-CoA reductase activity seemed to be at least partly due to the changes of HMG-CoA reductase mRNA levels. The level of HMG-CoA reductase mRNA in cells incubated in THDS-MEM decreased to 76.2% relative to the cells grown in FBS-MEM, while the level of reductase mRNA in cells incubated in THDS-MEM containing T₃ at a concentration of 10^(-6) M increased to 243.4% relative to the cells grown in FBS-MEM. The increase of HMG-CoA reductase mRNA level after T₃ treatment may have been due to the increased stability of reductase mRNA, because the transcriptional rate of the reductase gene did not change significantly in the presence or absence of T₃. These results indicate that T₃ stabilizes HMG-CoA reductase mRNA at the posttranscriptional level and regulates HMG-CoA reductase activity in a dose-dependent manner.