Recent studies have shown that metal ions can be released from dental amalgam or other dental materials, and can cause toxic effects on various cells. In this study, the effects of amalgam-conditioned culture medium (ACCM), components of amalgam (Ag+, Cu2+, Sn2+, Hg2+) and dental composite-conditioned culture medium (CCCM) on histamine release from human blood basophils (healthy subjects, n = 3) and tissue mast cells (n = 3) were analyzed. ACCM and CCCM were prepared using either fresh or 6-weeks-aged specimens. Of the metal ions tested, Ag+, and Hg2+ were found to induce histamine release from basophils (Ag+, 0.33 mM: 83 +/- 11% vs Hg2+, 0.33 mM: 100% vs control medium: 5 +/- 5%) and mast cells (Ag+, 0.33 mM: 91 +/- 16% vs Hg2+, 0.33 mM: 99 +/- 1% vs control: 2 +/- 1%), whereas no effects were seen with Cu2+ and Sn2+. Neither ACCM from freshly prepared amalgam nor ACCM from 6-weeks aged amalgam, produced histamine release in basophils or mast cells. Inductively coupled plasma atomic emission spectrometry (ICP) revealed that the Ag(+)- and Hg(2+)-concentrations in ACCM were below the range in which histamine release occurred. Similar to ACCM, no effects on basophils or mast cells were observed with CCCM. In summary, our data show that distinct metal ions present in dental amalgam, can induce (toxic) histamine liberation from basophils and mast cells. However, the amounts of metal ions released from amalgam apparently were too low, to cause histamine release.