Previous studies have shown that toxic reactions to direct-bonding adhesives can be demonstrated both in animals and in cell culture tests. These effects have also been shown with other related dental materials. The purpose of this study was to compare the relative toxicity of a number of common orthodontic adhesives and to determine, by means of a rapid, sensitive in vitro cell culture agar overlay test, how their toxicity changed with time subsequent to polymerization. Various othordontic bonding materials were tested either immediately or at various times up to 30 days after polymerization. The cells were stained with a vital dye (neutral red), the diameter of the area of unstained, nonviable cells was measured, and the results of three tests per sample were averaged and analyzed by means of Duncan's Multiple Range Tests. All materials were found to have some cytotoxic effect immediately after mixing, with the activator components of two "no-mix" materials exhibiting significantly higher toxicity (p less than 0.05) than other materials tested. The sealant materials showed a significantly greater toxicity than paste resins, both initially after mixing and after 30 days postpolymerization. If applicable to the clinical situation, these data indicate that care is needed particularly in handling liquid activators. Excess "polymerized" sealant, which may contain many nonreacted groups, should be carefully removed by scaling peripheral to the bracket bases, particularly in subgingival and interproximal areas.