Nuclear receptors are ligand-inducible transcription factors that can be classified into two major groups according to their DNA-binding properties. Members of the first group bind to DNA as dimers, either homo- or heterodimers; members of the second group are also able to bind as monomers. While the first group has been extensively studied biochemically, very little is known about nuclear receptors that bind and act as monomers. In this study, we compared the binding and transcriptional behaviour of ROR alpha (NR1F1) and ROR beta (NR1F2), two representatives of the subgroup of monomer-binding receptors. We show that although they are highly related in their amino acid structures, they display remarkably different binding behaviours. Furthermore, we provide evidence that ROR beta can efficiently activate transcription in vitro as a monomer.