Retinoic acid receptors appear to exert profound effects on vertebrate development by regulating the transcription of distinct sets of target genes within different cell types. Several lines of evidence are presented for the existence of multiple, cell type-specific nuclear proteins that function to differentially increase the binding affinity of the alpha retinoic acid receptor for a variety of response elements. These proteins, which we refer to as retinoic acid receptor coregulators, interact with the retinoic acid receptor via a common dimerization interface that overlaps with its ligand binding domain. These observations raise the intriguing possibility that coregulator proteins serve to restrict and/or direct the effects of retinoic acid receptors on patterns of gene expression during development.