Plaque formed during a 5-day xylitol or sucrose chewing gum diet was used as an irritating agent in bone and macrophage culture. The release of hydrolytic enzymes was monitored. The contents of protein, DNA, and ATP were analyzed, to characterize plaque formed during different dietary periods. The release of glycosidases and phosphatases was lower in the presence of xylitol plaque when compared with sucrose plaque as an immediate reaction in macrophage cultures at 3 h and also in bone cultures at 3 days. The results indicate that xylitol plaque had a less irritating effect on macrophages and bones in vitro than sucrose plaque according to the parameters used in this study.