Given the recent explosion of publications that employ microarray technology to monitor genomewide expression and that correlate these expression changes to biological processes or to disease states, the determination of the transcriptional regulation of these co-expressed genes is the next major step toward deciphering the genetic network governing the pathway or disease under study. Although computational approaches have been proposed for this purpose, there is no integrated and user-friendly software application that allows experimental biologists to tackle this problem in higher eukaryotes. We have previously reported a systematic, statistical model of mammalian transcriptional regulatory sequence analysis. We have now made crucial extensions to this model and have developed a comprehensive, user-friendly web application suite termed the Promoter Analysis Pipeline (PAP). PAP is available at: http:// bioinformatics.wustl.edu/webTools/portalModule/PromoterSearch.do.