In the present study we have investigated the effect of factors released by cells derived from porcine epithelial rests of Malassez (ERM) on bone resorptionin vitro. The osteolytic effect of these cells was tested by co‐culturing them with fetal rat calvariae and then measuring the cumulative change in calcium concentration of the culture medium. When ERM cells were cultured with calvariae for 4 days, there was a significant increase in calcium release from the bones compared with bones cultured without ERM. ERM cells alone did not change the calcium concentration of the culture medium. When calvariae there cultured in medium that had been collected from ERM cultures, significant bone resorption could also be obtained. Indomethacin (200 ng/ml), an inhibitor of prostaglandin synthesis, inhibited calcium release from control calvariae and from calvariae cultured with ERM. However, calvariae cultured in the presence of ERM and indomethacin released significantly more calcium than those cultured in the presence of indomethacin alone. Thus, factors other than PG account for the osteolytic effect of ERM. Other cells cultured from oral tissues, such as gingival fibroblasts and fibroblasts from periodontal ligament as well as rat osteosarcoma cells also stimulated calcium release from calvariae. These results show that many cell types have the capacity to release bone resorbing factorsin vitroand support the belief that under suitable conditionsin vivobreakdown of alveolar bone may be stimulated by tissues proximal to i