Discovering repetitive, interesting, and functional substructures in a structural database improves the ability to interpret and compress the data. However, scientists working with a database in their area of expertise often search for a predetermined type of structure, or for structures exhibiting characteristics specic to the domain. This paper presents methods for guiding the discovery process with domain-specic knowledge. In this paper, the Subdue discovery system is used to evaluate the bene- ts of using domain knowledge. The domain knowledge is incorporated into Subdue following a single general methodology to guide the discovery process. Results show using domain-specic knowledge improves the search for substructures which are useful to the domain, and leads to greater compression of the data. To illustrate these bene- ts, examples and experiments from the domain of computer programming, computer aided design circuit, and a series of articially-generated domains...