Historical Perspective. The formation of a specific complex between two strands of poly(uridylic acid) with one strand of poly(adenylic acid) in the presence of divalent cations was first described by Felsenfeld et al. (1957). Subsequently, triple-stranded complexes containing other combinations of polynucleotide strands were described including those belonging to the deoxyribose series [reviewed in Felsenfeld and Miles (1967), Wells et al. (1988), Cheng and Pettitt (1992b), and Sun and H61Sne (1993)]. These studies culminated in lowresolution, X-ray fiber-diffraction models for the (A)"-2(U)", (A)"'2(I)", and (A)"-2(T)" combinations (Arnott & Seising, 1974, and references cited therein). Further, a potential biological function for these structures was identified when they were found to inhibit RNA1 polymerase-mediated transcription in vitro (Morgan & Wells, 1968).Interest in triplexes revived following the discovery of singlestrand-specific SI endonuclease hypersensitive sites in the upstream regions of several eukaryotic genes (Larsen & Weintraub, 1982). These sites were mapped to (R)"-(Y)" sequences which, when subcloned into supercoiled plasmids, exhibited the same sensitivity toward SI nuclease [reviewed + This work was supported under NIH Grant GM 34504 to D.J.P.A Coordinates for the Y-RY triplexes containing G*TA (Accession No. 149D) and T-CG (Accession No. 177D) triples and the R-RY triplex (Accession Nos. 134D, 135D, 136D) have been deposited with the Protein Data Bank, Brookhaven National Laboratory, Upton, NY 11973, from whom copies can be obtained.