Until adhesiveness of dentin bonding agents and other restorative materials to dental structures can be assured, microleakage into resulting ''gaps'' and dentin permeability will remain major concerns in cases of pulpal irritation. The objectives of the present study were to (a) delineate the kinds and levels of metabolic cytotoxicity of the GLUMA and Scotchbond 2 systems as well as glutaraldehyde and 2-hydroxyethylmethacrylate, and (b) compare the effects of these same materials after diffusion through dentin discs approximately 0.5-mm thick. In monolayer cultures, glutaraldehyde was much more cytotoxic than 2-hydroxyethylmethacrylate. However, GLUMA sealer and Scotchbond 2 adhesive exhibited similar cytotoxicity in monolayer cultures. After diffusion through dentin, glutaraldehyde and 2-hydroxyethylmethacrylate effects were diluted 14.7 and 26.7 times, respectively. The postdiffusional effects of the GLUMA and Scotchbond 2 systems were not significantly different and less than those effects in monolayer cultures. This study should help in the evaluation of possible causes of pulpal irritation following restorative procedures.