We have developed a theoretical description of the amperometric response of ultramicroelect rode (UME) biosensors formed via enzyme entrapment. Our model allows for multiple enzymes and co-substrates, and results in a closed-form analytical expression for the steady-state current response of the disk ultramicroelectrode. It captures the effects of enzyme-entrapment domain size, species transport properties (which can be different in the polymer and surrounding electrolyte), enzyme kinetics, and axisymmetric diffusion. Assumptions inherent in the derivation are carefully explained, as are the resulting limits on the applicability of the results. The ability to theoretically predict the response of enzyme entrapped UMEs should enable improved design, operation, and data interpretation for this important class of biosensors. (c) 2007 Elsevier B.V.. All rights reserved.