In order to study the interactions and the photoreactions between psoralens and nucleic acid bases, model compounds were prepared in which a furocoumarin is linked to the base thymine or adenine by a flexible polymethylene chain of varying length. Models 6-11 of the two important drugs 5-methoxypsoralen 1 (5-MOP) and 8-methoxypsoralen 2 (8-MOP) were examined. All these models exhibit a high degree of intramolecular ring-ring stacking in water as revealed by UV and NMR spectroscopies. The photoreactions of the models were studied in relation with their ground state interaction properties. For the thymine-5-MOP models 6, a highly stereoselective intramolecular photoaddition between the 3,4 psoralen and the 5,6 thymine double bonds was observed at very low concentration leading to the cis-anti¹ adduct 1.5. A remarkable different behaviour was evidenced for the thymine-8-MOP models 7 for which photolysis of the pyrone ring occurs exclusively. This approach was extended to the study of compounds 19 in which the nucleoside thymidine is linked by a diester chain to a 5-MOP derivative. A totally regio, stereo and diasteroselective intramolecular photoaddition leads to the 3,4 cis-anti adduct 26 which can be obtained at the gram scale. Hydrolysis of the linking chain followed by methylation allows the obtention of the corresponding thymidine-5-MOP adduct 24. The adduct 31 possessing the syn¹ configuration was also prepared from model 30 in which the orientation of the thymidine and psoralen aromatic rings has been modified.