We have used high-density oligonucleotide arrays to study global circadian gene expression in Drosophila melanogaster. Coupled with an analysis of clock mutant (Clk) flies, a cell line designed to identify direct targets of the CLOCK (CLK) transcription factor and differential display, we uncovered several striking features of circadian gene networks. These include the identification of 134 cycling genes, which contribute to a wide range of diverse processes. Many of these clock or clock-regulated genes are located in gene clusters, which appear subject to transcriptional coregulation. All oscillating gene expression is under clk control, indicating that Drosophila has no clk-independent circadian systems. An even larger number of genes is affected in Clk flies, suggesting that clk affects other genetic networks. As we identified a small number of direct target genes, the data suggest that most of the circadian gene network is indirectly regulated by clk.