The results of empirical and semitheoretical potential function calculations have shown that fluorene derivatives with established carcinogenic activity can intercalate, in the Lerman sense, between the complementary pairs of cytidylyl-guanosine. The interaction energy is strongly dependent on the ionization state of the compounds studied. The optimized intercalation position depends on the position of substitution on the fluorene ring and to a lesser extent on the nature of the side chain. The intercalation effect explains the different biological activity of 2- and 4-substituted isomers of acetylaminofluorene.