The circadian rhythmicity of hormone secretion, body temperature and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity both centrally and in the periphery, however melatonin proficient Clock ¹⁹+MEL mutant mice retain melatonin rhythmicity, suggesting their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light/dark (LD) conditions both per2 and prokineticin2 (PK2) mRNA expression were rhythmic in the SCN of Clock ¹⁹+MEL mice. Expression of Bmal1 and npas2 was not altered, while per1 expression was arrhythmic. In contrast to the SCN, both per1 and per2 expression as well as that of Bmal1 in the liver and skeletal muscle, together with plasma corticosterone, were arrhythmic in Clock ¹⁹+MEL mice in LD. npas2 mRNA was also arrhythmic in the liver, but rhythmic in muscle. The Clock ¹⁹ mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homologue, possibly npas2, exists in the SCN. Nevertheless, the SCN of Clock ¹⁹+MEL mice cannot maintain liver and muscle rhythmicity through rhythmic outputs including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore liver and muscle, but not the SCN have an absolute requirement for CLOCK, with as yet unknown Clock independent factors able to generate the latter.