The technique of subtractive hybridization is used to enrich abundant cDNAs that differ between two cell populations. This approach is well suited for systems in which a homogenous cell population is activated in culture with an agent or factor that induces the transcription of genes that are either not present or at low abundance in the unactivated state. Whereas this scenario is the ideal model, models of comparison between heterogeneous cell cultures or even tissues have been analyzed by subtractive hybridization with success. The magnitude of success is directly related to the magnitude of the differential upregulation of relevant transcripts in the activated state over the unactivated state.