The importance of electrostatic interactions to the reaction between cytochrome c and cytochrome c oxidase is indicated most directly by the rapid increase in Km as ionic strength is increased. However, Chessa et al. (1980, Hoppe-Seyler's Z. Physiol. Chem. 361, 1077--1091) have recently found that a cytochrome c derivative trifluoroacetylated at all 19 lysine amino groups decreased the reaction rate between ferrocytochrome c and cytochrome c oxidase nearly as much as native ferricytochrome c, a known inhibitor that binds cytochrome c oxidase. They suggested that this was due to the formation of an inhibitory complex between trifluoroacetyl-cytochrome c and cytochrome c oxidase, which would argue against the importance of electrostatic interactions to the native complex. We have demonstrated that this apparent inhibition is in fact caused by a rapid electron transfer between native ferrocytochrome c and trifluoroacetyl-ferricytochrome c which decreases the concentration of native ferrocytochrome c, thus decreasing the reaction rate.