A biocatalytic fuel cell cathode operating with gas-phase air or oxygen is demonstrated. The cathode consisted of the oxygen-reducing enzyme laccase from Trametes versicolor and an osmium-based redox polymer mediator. These components were deposited with a small amount of citrate buffer solution onto a porous carbon-fiber support. The biocathode was combined with a Nafion electrolyte membrane and a conventional platinum anode to form a membrane-electrode assembly. The electrode reached current densities of 1 mA/cm(2) at 0.8 V (vs reference hydrogen electrode) when exposed to humidified oxygen or air but was unstable because of water loss from the cathode. Flow rate, humidification, and oxygen concentration of the cathode gas stream had a strong effect on stability but not on maximum current density. Cyclic voltammetry and electrochemical impedance experiments revealed that ionic conductivity in the cathode decreased as water was lost.