The transient current-potential response of the enzyme-catalyzed oxygen reduction reaction in biofuel cells is analyzed. The one-dimensional nonlinear reaction-diffusion equation is solved analytically using the homotopy method for deriving the substrate concentrations and current densities pertaining to chronoamperometric response. The time required to obtain the steady state has been obtained and the influence of film thickness, diffusion coefficients, and enzyme characteristics has been deciphered. The equations are shown to be valid for experimental data on mediated electron transfer reactions of redox polymers containing osmium complexes. The substrate concentrations and current densities for supported, gas-diffusion and flow through electrodes are also reported. (C) 2015 The Electrochemical Society. All rights reserved.