The periods of circadian clocks are relatively temperature-insensitive. Indeed, the per(L) mutation in the Drosophila melanogaster period gene, a central component of the clock, affects temperature compensation as well as period length. The per protein (PER) contains a dimerization domain (PAS) within which the per(L) mutation is located. Amino acid substitutions at the per(L) position rendered PER dimerization temperature-sensitive. In addition, another region of PER interacted with PAS, and the per(L) mutation enhanced this putative intramolecular interaction, which may compete with PAS-PAS intermolecular interactions. Therefore, temperature compensation of circadian period in Drosophila may be due in part to temperature-independent PER activity, which is based on competition between inter- and intramolecular interactions with similar temperature coefficients.