A circadian clock has been localized to the photoreceptor layer in the Xenopus laevis retina. This clock controls the rhythmic synthesis of melatonin, which results in elevated levels during the night and low levels during the day. The rate-limiting enzyme in melatonin synthesis in Xenopus laevis retina is tryptophan hydroxylase. A cDNA clone coding for Xenopus tryptophan hydroxylase was isolated, characterized, and used as a probe for analysis of tryptophan hydroxylase mRNA expression. Northern blot analyses of total retinal RNA show that the tryptophan hydroxylase message levels are low in the day and higher at night. The expression of tryptophan hydroxylase mRNA is under circadian control because rhythmic changes are also seen in constant darkness, with elevated levels during the subjective night. Nuclear run-on analysis during the first subjective day in constant darkness revealed that transcription initiation is low early in the day and increases throughout the day. Our observations suggest that the circadian clock modulates tryptophan hydroxylase gene expression. An understanding of how the circadian clock controls tryptophan hydroxylase expression may lead to a clearer understanding of the melatonin biosynthetic pathway, and possibly the clock itself.