We identify the RARα, RXRα and CRABPII domains required for the physical interaction of these proteins. On RARα and RXRα, the sequences correspond to the DEF and DE domains, respectively, but the interaction with CRABPII does not require the AF-2AD ‘core’. On CRABPII, two interacting domains are identified (NRID1 and NRID2), one of which contains the only enhancement transactivation domain of CRABPII. The interaction is ligand-independent and does not require the ligand-binding domain of CRABPII. These results further stress that interaction of CRABPII with the nuclear receptors defines a novel level of transcriptional control.