Hypersensitivity reactions in patients receiving metal-on-metal hip replacements have been attributed to corrosion products as observed by elevated cobalt and chromium ions in the blood. Although the majority of cases are reported in metal-on-metal, incidences of these reactions have been reported in the metal-on-polyethylene patient population. To date, no in vitro study has considered cobalt release for this bearing combination. This study considered four 28 mm and seven 52 mm diameter metal-on-polyethylene bearings tested following ISO standard hip simulator conditions as well as under established abrasive conditions. These tests showed measurable cobalt in all bearings under standard conditions. Cobalt release, as well as polyethylene wear, increased with diameter, increasing from 52 to 255 ppb. The introduction of bone cement particles into the articulation doubled polyethylene wear and cobalt release while alumina particles produced significant damage on the heads demonstrated by cobalt levels of 70,700 ppb and an increased polyethylene wear from a mean value of 9–160 mm3/mc. Cobalt release was indicative of head damage and correlated with polyethylene wear at the next gravimetric interval. The removal of third body particles resulted in continued elevated cobalt levels in the 52 mm diameter bearings tested with alumina compared to standard conditions but the bearings tested with bone cement particles returned to standard levels. The polyethylene wear in the bone cement tested bearings also recovered to standard levels, although the alumina tested bearings continued to wear at a higher rate of 475 mm3/mc. Cobalt release was shown to occur in metal-on-polyethylene bearings indicating damage to the metal head resulting in increased polyethylene wear. While large diameter metal-on-polyethylene bearings may provide an increased range of motion and a reduced dislocation risk, increased levels of cobalt are likely to be released and this needs to be fully considered before being widely adopted.