The present invention is directed to methods to identify test compounds that alter circadian rhythms of mammals, and more specifically, directed to methods for determining the ability of a test compound to alter hCKI delta and epsilon phosphorylation of a human Period protein. The present invention is also directed to a method for determining the ability of a test compound to selectively alter phosphorylation, interaction with, or alternatively degradation, of one or more human Period proteins relative to its ability to alter phosphorylation, interaction with, or alternatively degradation, of a different human Period protein.