In mammals, the circadian system is hierarchical — a brain pacemaker located within the suprachiasmatic nucleus (SCN) is responsible for regulating locomotor activity rhythms and for synchronizing peripheral oscillators [1,2]. Recent genetic evidence in mice indicates that the bHLH transcription factors CLOCK and NPAS2 have partially redundant functions within the SCN [3,4]. To further examine the roles of CLOCK and NPAS2, we generated CLOCK-deficient (Clock^−/−), NPAS2-deficient (Npas2^−/−) and double-mutant (Clock^−/−;Npas2^−/−) mice carrying the mPer2^Luciferase reporter gene [5]. We monitored the bioluminescence rhythms of tissue explants in culture and found that while CLOCK or NPAS2 is able to maintain SCN bioluminescence rhythmicity (Supplemental Data) [4], peripheral oscillators are arrhythmic without CLOCK. Thus, there are fundamental differences between the clock machinery of different tissues.