The biological response to prosthetic wear particles is thought to stimulate the bone loss that often leads to prosthetic joint failure. This in vitro study investigates how metal particles corrode under physiological conditions and how biological responses to particles may change as particles age. Cobalt chrome alloy (CoCr) and 316L stainless steel (SS) particles of a similar size, shape, and concentration to those found in revision tissues were used. The release of soluble metal (Co and Cr from CoCr particles and Fe from 316L SS) was markedly reduced with time under physiological conditions. CoCr particles released far more Co than Cr. The biological responses to aged and freshly produced particles were tested using human monocytes because wear particles are usually associated with this type of cell in the periarticular tissues. Aged particles of both metals were markedly less toxic to monocytes than freshly produced particles. Aged particles also appeared to stimulate the release of more IL-6 and prostaglandin E(2) from monocytes. The results show that CoCr and 316L SS particles become less toxic but may induce more bone resorbing mediators as they age in vivo. Copyright 2000 John Wiley & Sons, Inc.