A full-scale novel combined anaerobic/micro-aerobic and two-stage aerobic biological process is used for the treatment of an actual chemical synthesis-based pharmaceutical wastewater containing amoxicillin. The anaerobic system is an up-flow anaerobic sludge blanket (UASB), the micro-aerobic system is a novel micro-aerobic hydrolysis acidification reactor (NHAR) and the two-stage aerobic process comprised cyclic activated sludge system (CASS) and biological contact oxidation tank (BCOT). The influent wastewater was high in COD, NH3-N varying daily 4016-13,093 mg-COD L-1 and 156.4-650.2 mg-NH3-N L-1, amoxicillin varying weekly between 69.1 and 105.4 mg-amoxicillin L-1, respectively; Almost all the COD, NH3-N, amoxicillin were removed by the biological combined system, with removal percentages 97%, 93.4% and 97.2%, respectively, leaving around 104 mg-COD L-1, 9.4 mg-NH3-N L-1 and 2.6 +/- 0.8 mg-amoxicillin L-1 in the final clarifier effluent. The performance evaluation of the wastewater treatment plant (WWTP) by mathematical statistic methods shown that at most of time effluent can meet the higher treatment discharge standard. In addition, the fate of amoxicillin in the full-scale WWTP and the amoxicillin removal rate of each different removal routes in UASB, NHAR, CASS, BCOT and final clarifier processes are investigated in this paper. The results show that biodegradation, adsorption and hydrolysis are the major mechanisms for amoxicillin removal. (C) 2011 Elsevier B.V. All rights reserved.