Non-amalgam filling materials may release substances which have been shown to be toxic in cytotoxicity tests and implantation studies. However, results from systemic toxicity tests do not indicate any unacceptable risk to the patient's general health, but data for non-amalgam dental filling materials are scarce in comparison to amalgam. Although estrogen-like effects of one fissure sealant have been claimed, no conclusions can be drawn at present for the patient from these in vitro data because of the limitation of the test methods and materials used. Some components of composite resins/dentin adhesives and a resin-modified glass ionomer cement were mutagenic mainly in in vitro tests. Due to the limitations of the test systems and the comparatively high concentrations needed to elicit the reactions, no unacceptable risk can yet be derived from those data for the patient. However, a no-touch technique is recommended for the dental personnel. As with amalgam, local reactions of the pulp are not expected with alternative filling materials, if the pulp tissue is not exposed and if bacterial penetration is avoided. The latter requirement is still difficult to fulfill, especially for composite resin systems and related materials in posterior teeth situations. Slight gingival reactions to alternative filling materials and to amalgams are mainly attributed to plaque accumulation. From all these data it can be concluded that, for the time being, it is not possible to rank dental filling materials in respect to their biocompatibility, and it is evident that biocompatibility must be considered to the same extent for both amalgams and commonly used or recommended alternative filling materials.