Identification and characterization of differentially expressed genes may be an important first step toward the understanding of both normal physiology and disease. A multitude of techniques belonging to two main categories have been developed to identify the differences in gene expression between samples from different biological origin: selection techniques and global techniques. Whereas the selection techniques strive to identify specific differentially expressed genes, the global techniques analyze the total transcriptome or a major part of the RNA population in a defined biological material. By exploiting the known sequences of the adaptors used in suppressive subtraction hybridization technique, a strategy named novel rescue-suppression-subtractive hybridization was developed. It should facilitate the discovery of differentially expressed genes.