The transcriptome of the intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum was analyzed to understand gene expression patterns during this stage. The study used a DNA microarray to examine gene expression across 48 one-hour timepoints of the IDC. The results showed that at least 60% of the genome is transcriptionally active during this stage, with over 75% of genes activated only once during the IDC. The data revealed a continuous cascade of gene expression, starting with genes for general cellular processes and ending with Plasmodium-specific functions. Genes on the same chromosome are rarely co-regulated, while plastid genes are highly co-regulated and likely polycistronic. Comparative genomic hybridization between HB3 and 3D7 strains showed that differences are mainly in subtelomeric regions. The IDC transcriptome resembles a "just-in-time" manufacturing process, with gene induction occurring only when needed. The study provides the first comprehensive view of the timing of transcription during the IDC and serves as a resource for identifying new chemotherapeutic and vaccine targets. The data also show that genes involved in host cell invasion are expressed at the peak of the IDC. The study highlights the unique transcriptional regulation of P. falciparum, with a simple cascade of gene regulation that is unprecedented in eukaryotic biology. The results suggest that the parasite has evolved a specialized mode of transcriptional regulation to ensure the completion of the IDC. The study also identifies potential drug targets, including proteins involved in plastid functions and proteases involved in merozoite invasion. The findings provide insights into the molecular mechanisms of P. falciparum and may aid in the development of new chemotherapeutic and vaccine strategies.The transcriptome of the intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum was analyzed to understand gene expression patterns during this stage. The study used a DNA microarray to examine gene expression across 48 one-hour timepoints of the IDC. The results showed that at least 60% of the genome is transcriptionally active during this stage, with over 75% of genes activated only once during the IDC. The data revealed a continuous cascade of gene expression, starting with genes for general cellular processes and ending with Plasmodium-specific functions. Genes on the same chromosome are rarely co-regulated, while plastid genes are highly co-regulated and likely polycistronic. Comparative genomic hybridization between HB3 and 3D7 strains showed that differences are mainly in subtelomeric regions. The IDC transcriptome resembles a "just-in-time" manufacturing process, with gene induction occurring only when needed. The study provides the first comprehensive view of the timing of transcription during the IDC and serves as a resource for identifying new chemotherapeutic and vaccine targets. The data also show that genes involved in host cell invasion are expressed at the peak of the IDC. The study highlights the unique transcriptional regulation of P. falciparum, with a simple cascade of gene regulation that is unprecedented in eukaryotic biology. The results suggest that the parasite has evolved a specialized mode of transcriptional regulation to ensure the completion of the IDC. The study also identifies potential drug targets, including proteins involved in plastid functions and proteases involved in merozoite invasion. The findings provide insights into the molecular mechanisms of P. falciparum and may aid in the development of new chemotherapeutic and vaccine strategies.