In simpler times, the driving gears of the circa 24-hour circadian clock were thought to consist of positively acting transcription factors that cause transcription of a gene whose protein then fed back to interfere with action of the positive elements and to inhibit its own transcription. Now, Shearman et al . (see the news story by Barinaga) show that the mammalian circadian clock, as was shown recently for the Drosophila clock as well, actually has two more "gears." The negative element is CRY, which interferes with the positive action of the heterodimer CLOCK and BMAL1. The authors now show that PER2 is a positive regulator of BMAL1, and CRY is a negative regulator of PER2. The next step will be to understand how this intricate oscillator keeps circadian time. Shearman, L.P., Sriram, S., Weaver, D.R., Maywood, E.S., Chaves, I., Zheng, B., Kume, K., Lee, C.C., van der Horst, G.T.J., Hastings, M.H., and Reppert, S.M. (2000) Interacting molecular loops in the mammalian circadian clock. Science 288 : 1013-1019. [Abstract] [Full Text] Barinaga, M. (2000) Two feedback loops run mammalian clock. Science 288 : 943-944. [Summary] [Full Text]