Retinoic acid receptors (RARs) are hormone-regulated transcription factors that play multiple roles in vertebrate development and differentiation. Three isotypes of RARs, α, β, and γ, are encoded by distinct genetic loci and possess distinct transcriptional properties. Typically, RARα represses target gene transcription in the absence of hormone, whereas RARβ and γ fail to repress under these conditions. This inability of RARβ and RARγ to repress transcription is due to intramolecular interactions between helix 3 and helix 12 of the hormone binding domains of these isotypes that inhibit corepressor binding while favoring coactivator binding. We report here that the converse ability of RARα to repress requires the integrity of the receptor F domain, a domain that maps C-terminal to helix 12, varies in sequence among different nuclear receptors, and is of poorly understood function. The F domain appears to help stabilize helix 12 of RARα in a more open position that enhances corepressor binding and inhibits coactivator binding in the absence of hormone. Intriguingly, the RARα F domain is isotype autonomous in its function. We speculate that the RARα F domain may dock elsewhere on the receptor surface, and this intramolecular interaction may maintain RARα helix 12 in an open, repression-competent conformation.