Recent data suggest that distinct metal ions can be released from dental alloys or other biomaterials, and may cause toxic effects on various cells. In this study, the effects of 14 metal ions on histamine release from human blood basophils (n = 4), isolated tissue mast cells (lung n = 8, uterus n = 2, skin n = 1, gingiva n = 1), the basophil cell line KU-812, and the mast cell line HMC-1 were analyzed. Of the 14 metal ions, Ag + (0.33 mM) and Hg 2+ (0.33 mM) were found to induce release of histamine in blood basophils, KU-812, mast cells, and HMC-1. The effects of Ag + and Hg 2+ were dose dependent and were observed within 60 min of incubation. In primary mast cells and basophils, Au 3+ (0.33 mM) also induced histamine release, whereas no effects of Au 3+ on HMC-1 or KU-812 cells were seen. The other metal ions showed no effects on primary or immortal cells within 60 min. However, Pt 4+ (0.33 mM) induced histamine libera-tion in HMC-1 and lung mast cells after 12 h. The Ag + -and Hg 2+ -induced rapid release of histamine from HMC-1 was associated with ultrastructural signs of necrosis, but not apoptosis. In contrast, prolonged exposure to Pt 4+ (0.33 mM, 14 h) induced apoptotic cell death in HMC-1 cells, as assessed by electron microscopy and DNA analysis. Together, certain metal ions induce distinct cytopathogenic effects in mast cells and basophils. Whereas Ag + , Hg 2+ , and Au 3+ cause direct toxicity, Pt 4+ causes cell death through induction of apoptosis. Whether such effects contribute to local adverse reactions to metal-containing biomaterials in vivo remains to be determined.