The effects of the position in the membrane of the doxyl group on the rate of reduction by external ascorbate were studied in large unilamellar liposomes. The key factor increasing the rate of reduction was the degree of partitioning of the nitroxide into the aqueous phase; the doxyl group's proximity to the surface of the membrane was not a major factor. Consistent with the latter finding, factors that increased the rate of membrane permeation by ascorbate did not have major effects on the observed rates of reduction. We conclude that in this system the external aqueous medium is the primary site of reduction of the doxyl stearates and the doxyl stearates are in effective equilibrium between the membrane and aqueous phases.