No valid animal or in vitro model exists to assess the potential mucosal irritancy of dental materials. However, recently, a commercially available model system based an a recombined co-culture of human fibroblasts and human epithelial cells has been introduced for evaluating the time-dependent irritancy of cosmetic products. Cell viability and prostaglandin E(2) (PGE(2)) release from the cells were used as markers for the irritative potential of test materials. The objective of the present study was to evaluate the suitability of this model for monitoring the irritative potential of metals and cast alloys used in dentistry. The human fibroblast-keratinocyte co-cultures were exposed to test specimens fabricated from copper, zinc, palladium, nickel, tin, cobalt, indium, a high noble cast alloy, and from a dental ceramic. Cell survival rates decreased after exposure to copper (14-25%), cobalt (60%), zinc (63%), indium (85%), nickel (87%), and the non-oxidized and oxidized high noble cast alloy (87%/90%) compared to untreated control cultures. Dental ceramic, palladium and tin did not influence cell viability. In parallel, the PGE(2) release was continuously monitored up to 24 h using a competitive displacement enzyme immunoassay. PGE(2) release increased most highly in the cultures exposed to copper (6-25 fold), cobalt (7 fold), indium (4 fold), and zinc (2 fold) compared to untreated control cultures. The PGE(2) determination proved to be a non-destructive method for continuous monitoring of cell reactions in the same culture. The model used seems promising for evaluating the time-dependent mucosal irritancy of dental cast alloys.