Statement of problem Oral metal exposure has been associated with systemic and local adverse reactions, probably due to elemental release from the alloys. Although supraphysiological concentrations of salts from dentally applied metals can activate innate cells through TLR4 (Ni, Co, Pd) and TLR3 (Au), whether direct exposure to solid alloys can also trigger innate immune reactivity is still unknown. Purpose The purpose of this in vitro study was to determine whether dental cast alloy specimens can activate innate cells and influence their responsiveness to bacterial endotoxin. Material and methods Human monocyte-derived dendritic cells (MoDC) and THP-1 cells were cultured on top of different alloy specimens (Ni-Cr, Co-Cr, Pd-Cu, Pd-Ag, Ti-6Al-4V, amalgam, gold, and stainless steel) or in alloy-exposed culture medium with or without endotoxin (lipopolysaccharide [LPS]; Escherichia coli 055:B5). Interleukin-8 (IL-8) production was used as the parameter for innate stimulation and evaluated by enzyme-linked immunosorbent assay after 24 hours of culture. The statistical significance of the effects of various casting alloys on the secretion of IL-8 was analyzed by using the nonparametric Wilcoxon rank sum test (α=.05). Results Dental cast alloys induced IL-8 production in MoDC and THP-1 cells, with Au and Pd-Cu providing the strongest stimulation. The alloy-exposed culture media tested contained sufficient stimulatory metal ions to induce detectable IL-8 production in THP-1 cells, except for the Ni-Cr and stainless steel exposed media. Au and Pd-Cu alloys were also most effective in potentiating LPS responsiveness as measured by IL-8 production. Conclusions Using an in vitro culture system to expose MoDC and THP-1 cells to different alloy specimens this study showed that contact with the solid alloys, in particular when they contain Pd or Au, can trigger innate immune responses and augment responsiveness to bacterial endotoxin.