The signals that determine activation and repression of specific genes in response to appropriate stimuli are one of the most important, but least understood, types of information encoded in genomic DNA. The nucleotide sequence patterns, or motifs, preferentially bound by various transcription factors have been collected in databases. However, these motifs appear to be individually too short and degenerate to enable detection of functional enhancer and silencer elements within a large genome. Several groups have proposed that dense clusters of motifs may diagnose regulatory regions more accurately. Cluster-Buster is the third incarnation of our software for finding clusters of pre-specified motifs in DNA sequences. We offer a Cluster-Buster web server at http://zlab.bu.edu/cluster-buster/.