Noninvasive opioid delivery systems that provide rapid pain relief offer advantages for outpatients with high-intensity, rapid-onset pain. fentanyl effervescent buccal tablets (FEBT) employ a novel delivery system that uses an effervescence reaction to enhance the rate and efficiency of oral transmucosal fentanyl absorption. Enhanced absorption of fentanyl is considered to be caused primarily by dynamic shifts in pH within the microenvironment lying between a dissolving tablet and the buccal mucosa. The initial drop in pH is a result of the dissolution of citric acid, which combines with bicarbonate to form carbonic acid. Carbonic acid dissociates into carbon dioxide and water. As carbon dioxide dissipates, the pH increases. The initial drop in pH favors the dissolution of fentanyl citrate, the ionized form of fentanyl, whereas the subsequent increase in pH favors the formation of nonionized fentanyl. Nonionized fentanyl prefers to associate with the more lipophilic molecules in the buccal mucosa rather than stay in solution surrounded by water molecules. The dynamic changes in pH that occur on the surface of FEBT as they dissolve can be measured in vitro. Pharmacokinetic studies in healthy volunteers have demonstrated more rapid and more complete fentanyl absorption with effervescent buccal delivery compared with noneffervescent buccal delivery. Controlled clinical studies in patients with high-intensity, rapid-onset pain are the next step in defining the clinical utility of this enhanced buccal absorption of fentanyl.