Abstract 1. 1. The kinetics of the oxidation of ferrocytochrome c by cytochrome c oxidase were studied spectrophotometrically by observing the rate of decrease in optical density at the α, β, or γ band of ferrocytochrome c as the reduced cytochrome c is oxidized. 2. 2. It was observed that the reaction remains first order with respect to the concentration of ferrocytochrome c, even with concentrations of ferrocytochrome c as high as 130 μ M . However, the first-order velocity constant was found to vary with the concentration of total cytochrome c (oxidized plus reduced) in the reaction mixture. Further purification of the cytochrome c did not alter the results. 3. 3. The results can best be explained by assuming an inhibitory effect of cytochrome c (either oxidized or reduced) on the reaction. 4. 4. This inhibitory effect of cytochrome c can explain a number of discrepancies previously apparent in studies of the kinetics of cytochrome c oxidase activity.