Stearoyl-CoA desaturase activity is encoded by two highly homologous genes, SCD1 and SCD2, which show tissue-specific expression and regulation. SCD1, which is expressed in the liver, showed a marked diurnal variation with the highest expression during the feeding period. Treatment of mice with the peroxisome proliferator clofibrate, which induces several lipid metabolizing enzymes, increased both the enzyme activity and mRNA level in the liver, indicating regulation at the transcriptional level. The highest expression of both SCD1 and SCD2 was found in brown adipose tissue, which was slightly down-regulated by feeding a fat-free diet.