The Drosophila engrailed gene product (En) is a homeodomain-containing protein that contributes to segmental patterning. In transfection assays it acts as a transcriptional repressor. We show that En is an active repressor, blocking activation by mammalian and yeast activators that bind to sites some distance away from those bound by En. Active repression is distinct from the effects of passive homeodomain-containing proteins, which repress when competing with activators for binding sites and activate when competing with En. Active repression activity maps outside the En homeodomain, and this activity can be transferred to a heterologous DNA binding domain.