SIGNALLING by all-trans retinoic acid is mediated through RXR-RAR retinoid receptor heterodimers(1,2), in which RXR has been considered to act as a transcriptionally silent partner(3-5), However, we show here that in cultured NB4 (ref. 6) human acute promyelocytic leukaemia(7-9) cells treated with either an RAR-alpha-selective agonist alone, or certain RAR-alpha antagonists in combination with an RXR agonist, receptor-DNA binding is induced in vivo, resulting in expression of the target genes of retinoic acid as well as acute promyelocytic leukaemia protein (PML) relocation to nuclear bodies(10-12) and differentiation before apoptosis, These results indicate that RAR-alpha ligands can induce two separate events : one enables RXR-RAR-alpha heterodimers to bind to DNA in vivo and allows RXR agonists to act; the other induces transcriptional activity of RAR-alpha. The availability of receptor-specific synthetic retinoids that can induce distinct receptor functions has potential in extending the therapeutic repertoire of retinoids.