Nuclear hormone receptors are believed to modulate target gene expression by interacting with the general transcriptional machinery of the cell. We demonstrate here that two otherwise closely related members of the nuclear hormone receptor family, retinoid acid receptors (RARs) and retinoid X receptors (RXRs), exhibit significant differences in their interactions with the transcriptional machinery. RARs display a strong constitutive interaction with transcription factor II-B (TFIIB) that requires the TFIIB C-terminus, whereas RXR exhibits a weaker, hormone-stimulated interaction with the TFIIB that maps outside of the TFIIB C-terminus. Use of a dominant-negative mutant of TFIIB suggests that the TFIIB interaction is essential for full transcriptional activation by RXR.