The Multi-stage Reversing-flow Bioreactor (MRB) which utilizes new biological interaction for organic substrate removal in wastewater has been developed. MRB has several stages, one stage consists of a downflow aeration vessel (AV) and an upflow biological reaction vessel (BV). Successful accumulation of self granulated sludge (SGS) can be achieved in BV. The biological interaction between sulfate reducing bacteria and sulfide oxidizing bacteria (Beggiatoa) is considered to contribute to SGS formation. The SGS is 2-10 mm in diameter and can be maintained in BV with upflow space velocity of 144 ro/day. Pilot plant study was conducted to demonstrate the performance of the MRB. The influent was municipal primary effluent. The total hydraulic retention time was 4.5 hours including the final solid-liquid separation in the last BV. The effluent quality was as fine as that of the conventional activated sludge process. The MRB has several advantages over the conventional biological wastewater treatment such as lower energy requirement, less sludge production, and no necessity for a final settling tank.