We studied the polarographic reduction of quinones in aqueous/organic mixtures with dielectric constants (ε) from 78.4 down to 47. Added organic co-solvents were either protic or aprotic. The increase in polarographic half-wave potential,E1/2, with decliningεwas successfully fit to the Born equation down toε≈ 55. Cu2+and ubiquinone0were reduced in a single two-electron step that was moreε-sensitive when the added organic co-solvent was aprotic. Naphtho- and anthraquinone were reduced in two successive one-electron steps that were influenced identically by protic or aprotic organic co-solvents. The product of the first reduction wave was neutral semiquinone (·QH), which surprisingly, had to be protonated to ·QH2+before reduction in the second wave. Except forrH+, radii derived from fitting ourE1/2vsεresults to the Born equation were too small; in other words, non-electrostatic effects destabilized the oxidized species, greatly enhancing the Born electrostatic increase inE1/2with decliningε. Additionally, forε< 55, we observed deviation from the Born equation, which may be due to changes in solvent structure and dynamics, and solvent-solute interactions. Finally, we studied quinones incorporated into phosphatidyl choline sonicated bilayer vesicles: Ubiquinone0had two distinct irreversible two-electron reduction waves, one due to a population bound at the membrane surface, and another (whoseE1/2was negatively shifted by 150 mV) due to a population localized in the membrane interior. Ubiquinone10had a single irreversible two-electron reduction wave that was 250 mV more negative than the UQ0membrane-interior population.