THE thyroid-hormone receptors are hormone-dependent transcription factors that control expression of many target genes(1,2). This regulation is presumably a consequence of hormone-dependent contacts between the receptors and the basal transcription machinery(3). We used the yeast two-hybrid system(4,5) to identify a candidate human transcriptional mediator that interacts with both the thyroid-hormone receptor and the retinoid-X receptor in a ligand-dependent fashion. This protein, Trip1 (for thyroid-hormone-receptor Interacting protein), shares striking sequence conservation with the yeast transcriptional mediator Sug1 (refs 6, 7). Here we show that Trip1 can functionally substitute for Sug1 in yeast, and that both proteins interact in vitro with the thyroid-hormone receptor, acid with the transcriptional activation domains of yeast GAL4 and of herpes virus VP16.