The issue of the biologic significance of metal ion release is addressed by reviewing the answers to five questions: what is released, how much is released, where do the ions go, what can they do, and what have they done? Data are presented to demonstrate that ions are released but not necessarily in proportion to the alloy composition. Nickel and cobalt bind to serum albumin, whereas chromium is released with a valence of +6 and binds to red blood cells. Tissue levels of chromium and titanium are often very high, indicating that these elements may form stable complexes that remain in local tissues. The results of chemical analysis of urine from animals exposed to metal ions from injection of salts or in vivo corrosion demonstrate a rapid excretion of nickel and cobalt; excretion of chromium is slow and represents a small percentage of the total to which the animal is exposed. The biological reactions of toxicity, metal sensitivity, and oncogenicity are discussed from the point of view of what they have been shown to do in laboratory and animal experiments. The limited number of clinical reports of these reactions are also reviewed. These issues are discussed in light of the need for future research and for the development of standard test methods for characterization of porous implant materials and the biological reactions to these materials.