4,6,4'-Trimethylangelicin, a well-known effective photosensitizer described as a pure monofunctional reactant with DNA, can induce interstrand cross-links in mammalian cell DNA in vivo (about 15% relative to 8-methoxypsoralen), as observed using alkaline elution and Chinese hamster ovary cells. Experiments performed using the two-step irradiation method and HeLa cells support these data. In contrast with 4,6,4'-trimethylangelicin, 4'-methylangelicin and 4,4'-dimethylangelicin do not form interstrand cross-links. These results are consistent with those recently reported by Chen et al. (X. Chen, J. Kagan, F. Dall'Acqua, D. Averbeck and E. Bisagni, J. Photochem. Photobiol. B: Biol, 22 (1994) 51-57) using pBR322 and M13 DNA. The cross-linking ability of 4,6,4'-trimethylangelicin does not seem to be related to a particular feature of these DNAs but to the compound itself.