Antibiotic resistance genes can be found on the same mobile genetic elements as genes coding for resistance to metals such as mercury (Hg). Amalgam restorations contain ca. 50% Hg and, therefore, it could be expected that exposure to such dental restorative materials may promote Hg resistance and thereby antibiotic resistance. An in vitro biofilm model was used to grow microcosm dental plaques on enamel or amalgam substrata. The number and proportion of Hg-resistant organisms over time were determined by viable counts. Microcosm dental plaques grown in the presence of amalgam had a higher number and proportion of Hg-resistant bacteria than those grown on enamel. The levels of these Hg-resistant bacteria remained elevated for a period of 48 h, however after 72 h the proportions returned to baseline levels. Of the 42 Hg-resistant bacteria isolated, 98% were streptococci, with Streptococcus mitis predominating. A high proportion of the Hg-resistant isolates (71%) were also resistant to a range of antibiotics, with resistance to tetracycline being encountered most frequently. The results of this in vitro study indicate that placement of amalgam restorations may play a role in promoting the levels of Hg- and antibiotic-resistant bacteria present in the oral cavity.