The broad spectrum of physiological activities of retinoids is mediate d by two types of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Though they have 9-cis retinoic acid as a common ligand, the amino acid sequence of their ligand binding domains is only distantly related (27%). This fact makes it probable that the ligand binding pockets of RARs and RXRs differ significantly with respect to their three dimensional structure. Therefore, one can expect that selective ligands for these receptor subclasses do exit. A clear example of a naturally existing RAR-selective retinoid is all-trans retinoic acid. Here we report on two synthetic retinoids which are very closely related to retinoic acid in structure yet show good receptor subclass selectivity. These compounds have a saturated double bond in the polyene side chain between either the 7, 8 or 9, 10 carbon atoms and are highly RAR or RXR selective, respectively (as shown by receptor binding, transactivation activity and the ability to induce RXR homodimer formation). In addition, we present compounds of the synthetic arotinoid class which are highly RAR selective. Interestingly the corresponding '9-cis analogs' are not able to bind or activate RXR alpha and show greatly reduced activity on the RARs.