Homopurine/homopyrimidine (PuPy) repetitive duplex sequences can form intramolecular triplexes (H-DNA) or intermolecular triplexes with a third strand in a sequence-specific manner. 2. Such sequences are present in natural genomes within 5'- and 3'-flanking sequences and coding regions of genes. Triplex DNA structures have been detected in vitro and in vivo and have been immunolocalized to chromosomes by triplex-specific monoclonal antibody approaches. 3. Intermolecular triplex formation represses gene expression at the transcriptional level and is also useful in genomic mapping, gene cloning, sequence-specific drug delivery, and selective modulation of gene expression.