Beta-quartz glass-ceramic inserts are a recent attempt to counteract some of the detrimental mechanical properties of resin composites by decreasing polymerization shrinkage and increasing wear resistance. The purpose of this study was to evaluate how manipulation, contamination, and disinfection would affect the resin composite-beta-quartz insert interface, as determined by microleakage. Seven groups (n = 10) of Class V cavity preparations were placed in extracted human molar teeth and restored with a microfilled resin composite and beta-quartz insert. In six groups, contamination or disinfection - latex glove, bare finger, human saliva, 95% ethanol, or LpHse disinfectant - was applied to the insert prior to placement. Latex gloves, bare fingers, and saliva were found to have a detrimental effect on the insert-resin composite interface that could compromise the longevity of the restoration.