Fragmentation reactions upon electron attachment to 5-fluorouracil with CH2R substituents at N1 have been evaluated by means of density functional calculations. The present results show that electron attachment to R = F, HC=O or CN derivatives follows a stepwise pathway with radical anions as intermediates. For these compounds, the most stable species formed is the pi radical anion which bears an unpaired spin density at the C6=C5-C4=O pi-conjugated system of the uracil ring. Cleavage of the N1-CH2R or N1CH2-R bond of these intermediates proceeds through the mixing of the pi and sigma states by means of proper geometrical fluctuations along the reaction coordinate. No sigma radical anion could be characterised on any of these sigma basal potential surfaces. A noticeable decrease in the activation energy for the N1-CH2R bond dissociation was observed for R = H-C=O or CN. Therefore, such derivatives with unsaturated groups positioned vicinal to the N1-C1' bond are identified as targets for the development of novel radiation-activated antitumour drugs. On the other hand, the electron transfer to the compounds with R = Cl, Br is dissociative, i.e. it occurs without the mediation of radical anions. For compounds with R = halides or R = NO2, the fragmentation of the N1CH2-R bond is the preferred dissociation pathway.