The concept of bioreductive alkylation as a mechanism of action of aziridinylquinoid anticancer agents has been investigated by the use of electrochemical techniques. Properly substituted aziridinylquinones are activated by an electrochemical step (reduction of the quinone function), followed by protonation of the aziridinyl moiety to the alkylating species. The influence of substitution on quinone reduction, on protonation and on subsequent opening of the aziridines (prior to and after quinone reduction) has been examined. A series of mono- and poly(1-aziridinyl)-quinones has been synthesized and analyzed by direct current (d.c.) polarography. The half-wave potential (E1/2 value of the quinone reduction and the pKred and pKred2 (reflecting the ease of protonation at the mercury electrode of one and two aziridinyl rings, respectively) were used in a Hammett type QSAR analysis. A linear relationship between E1/2 and the electronic substituent constant ¿p was obtained for simple quinones. Deviations from linearity were observed, due to steric and/or resonance interactions which influence quinone reduction, with amino- and halogen-substituted quinones. Unknown ¿p values could be calculated. Relationship between pKred2 and some physical-chemical parameters show that electronic and steric properties of quinone substituents affect pKred2. In addition, the formation of a hydrogen bond between the quinone substituent and the adjacent aziridinyl ring (which may thwart aziridine protonation) and the presence of a methyl substituent at position 2 of the aziridine (which facilitates protonation) are of importance. Results of this study have lead to a better knowledge of the individual substituents with respect to their electronic and steric influences on quinone reduction and aziridine protonation, which may be of importance if these processes play a decisive role in cytostatic activity as well as toxicity.