Regulation of the activity state of the hepatic BCKDC during the light-dark cycle differs markedly in male and female rats. Male rats show little evidence of a diurnal rhythm in the regulation of the complex. However, female rats exhibit a profound diurnal rhythm in the activity state. Regardless of gender most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats al the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Changes in blood levels of branched-chain o-keto acids, only known regulators of BCKDH kinase, did not correlate with changes in BCKDC activity state in female rats. Rather it appears that the greater BCKDC phosphorylation is due to a stable increase in BCKDH kinase activity. Western blot analysis indicates that the increased expression of BCKDH kinase protein is responsible for the increase in BCKDH kinase activity. Thus, this study provides evidence for a gender-specific difference in the regulation of branched chain amino acid olisni. A diurnal variation in expression of BCKDH kinase appears to be ;in important factor in the difference in the regulation of BCKDC1 activity between male and female rats.