In the Drosophila melanogaster circadian system, daily oscillations in the abundance of the central clock proteins PERIOD (PER) and TIMELESS (TIM) are maintained by posttranslational modifications that regulate their stability and nuclear entry. My studies characterize a novel role for the p90 ribosomal S6 kinase (S6KII) in modulating the clock at the behavioral and molecular level. S6KII null mutants (S6KII^ign) exhibit short-period locomotor activity rhythms. Consistent with a short period, S6KII^ign flies show increased anticipation of the lights-on transition. I demonstrate that S6KII function is required within clock cells for normal behavioral rhythmicity. I show that decreased S6KII results in increased PER-mediated repression, consistent with the increased PER protein and decreased per mRNA levels that I document in S6KII^ign flies. S6KII exhibits physical and genetic interactions with the known clock kinase CASEIN KINASE 2 (CK2). My data support a model for S6KII function in the molecular oscillator in which S6KII negatively regulates CK2 and thereby PER-mediated feedback repression. This produces an abbreviated repression phase, and consequently, a short period molecular oscillator. I concede that alternatively, S6KII may act directly on the PER/TIM oscillator or through other targets. My in vivo structure/function analysis of S6KII in the clock cells reveals important domains for its modulation of locomotor activity behavior. I demonstrate that the C-terminal kinase of S6KII is required for rescue of short-period locomotor activity rhythms while the N-terminal kinase is dispensable. The importance of the C-terminal kinase is supported by a correlation between phosphorylation at the kinase’s autophosphorylation site and the ability of a particular S6KII transgene to rescue shortperiod behavior. My studies show that ERK binding to and phosphorylation of S6KII is required for behavioral rescue and promotes C-terminal autophosphorylation. I provide the first in vivo evidence of serial phosphorylation and kinase activation along the S6KII protein. I postulate that ERK binding to S6KII activates the C-terminal kinase and promotes S6KII modulation of the circadian clock via negative regulation of CK2.