In the last decade enormous advances in life sciences have been possible due to the information obtained from DNA sequencing projects. The optimal interpretation and analysis of genome sequence data requires the precise annotation and classification of proteins deduced from open reading frames, which is usually done with the help of family-specific signatures. Here we report a novel profile for the IclR type of transcriptional activators and repressors. In contrast to profiles for other families of transcriptional regulators, the new IclR profile is located outside the helix-turn-helix DNA-binding motif. We provide evidence that the new profile is more specific than any of the existing signatures for this family of regulators. More than 500 representatives of this family were identified with this profile. A database on bacterial regulators (http://www.bactregulators.org) was built to compile and regroup the sequences with the aid of the new profile.