Using the anode effluent to compensate the alkalinization in a bio-cathode has recently been proposed as a way to operate a microbial fuel cell (MFC) in a continuous and pH neutral way. In this research, we successfully demonstrated that the operation of a MFC without any pH adjustments is possible by completing the liquid loop over cathode and anode. During the complete loop operation, a stable current production of 23.2 +/- 2.5 A m(-3) MFC was obtained, even in the presence of 3.2-5.2 mg O(2) L(-1) in the anode. The use of current collectors and subdivided electrical circuitries for relative large 2.5-L-scale MFCs resulted in ohmic cell resistances in the order of 1.4-1.7 mOmega m(3) MFC, which were comparable to values of ten times smaller MFCs. Nevertheless, the bio-cathode activity still needs to be improved significantly with a factor 10-50 in order achieve desirable current densities of 1,000 A m(-3) MFC.