This study examined the clinical wear performance of second-generation metal-on-metal (M-M) total hips and evaluated the cellular reaction to, and characteristics of, the wear particles. Twenty cobalt chrome (CoCr) M-M THRs were studied, including ten Metasul conventional total hips (THRs), and ten McMinn surface replacements (SRs). As in the first-generation M-M hips, wear ranged from undetectable to 32 μm in the SR femoral shells (ave 15.7 ± 14 μm) and from undetectable to 19 μm in the THR balls (ave 10.1 ± 7 μm). Self-polishing of third body scratches was evident. Two THRs exhibited clusters of micropits, which had been described on first-generation M-M hips but these did not appear to correlate with accelerated wear. CoCr particles were either dense or amorphous and were mostly in the nanometer size range. There were generally fewer macrophages in the tissues than seen with M-PE THRs, and there was a more inflammatory response to bone cement particles compared with metal particles. Nevertheless, the long-term response to these very small CoCr particles should be monitored.