Damage induced by a single psoralen-modified triple helix-forming oligonucleotide has been reported to be efficiently repaired in human cells. In this study we investigated a set of psoralen coupled oligonucleotides introducing multiple lesions into the target DNA. A simian virus 40 (SV40) shuttle vector was in vitro treated with different triple helix-forming oligonucleotides and UVA radiation, leading to double psoralen adducts at the supF mutational target gene of the plasmid. After passage in the Raji human cell line the recovered vector was analysed in an indicator bacterial strain. The results show that double psoralen adducts, located at both ends of a long triple helix, cannot be repaired efficiently in human cells.