The widespread introduction of materials for direct bonding into practices and the numerous reports of a variety of toxic reactions to similar materials prompted a study of the toxicity of six adhesives in an animal model. Thirty-nine hamsters were employed to evaluate responses of skin, oral mucosa, and gingiva, sites of possible contamination by adhesives in clinical use. Animals were treated topically with separate components of adhesives. Adhesives were also allowed to polymerize on and remain in contact with tissues. Test sites were examined grossly and histologically and evaluated for toxic response. The monomer component of one adhesive consistently caused gross irritation and histologic inflammation in twelve animals (p less than 0.001) in which it was used. Other adhesives and components did not have this effect. This adhesive was withdrawn from the market and modified at about the same time these experiments were performed. Similar results have not been observed with the modified product. Clinicans should recognize the potential for reaction to adhesives and realize that products with a toxic potential can reach the market. They should be prepared to change adhesives should reactions to one be observed. They should further recognize that absence of reaction in any test system does not preclude reaction in clinical use.