Signal transduction pathways control most cellular activities in living cells ranging from regulation of gene expression to fine-tuning enzymatic activity and controlling motile behavior in response to extracellular and intracellular signals. Because of their extreme sequence variability and extensive domain shuffling, signal transduction proteins are difficult to identify, and their current annotation in most leading databases is often incomplete or erroneous. To overcome this problem, we have developed the microbial signal transduction (MiST) database (), a comprehensive library of the signal transduction proteins from completely sequenced bacterial and archaeal genomes. By searching for domain profiles that implicate a particular protein as participating in signal transduction, we have systematically identified 69 270 two- and one-component proteins in 365 bacterial and archaeal genomes. We have designed a user-friendly website to access and browse the predicted signal transduction proteins within various organisms. Further capabilities include gene/protein sequence retrieval, visualized domain architectures, interactive chromosomal views for exploring gene neighborhood, advanced querying options and cross-species comparison. Newly available, complete genomes are loaded into the database each month. MiST is the only comprehensive and up-to-date electronic catalog of the signaling machinery in microbial genomes.