The hydrolysis of phenobarbital is decelerated in alkaline solution by betacyclodextrin. The betacyclodextrin inhibits the degradation of phenobarbital up to 1.5 fold in the system containing 1% betacyclodextrin. The degradation mechanism in systems containing betacyclodextrin is the same that in system without complexing agent, although the rate constants are different. The pH dependence of the hydrolysis rate deceleration is compared with the ionization percent of betacyclodextrin. The results indicate that a direct relationship does not exist between the ionization of betacyclodextrin. It seems reasonable therefore that the phenobarbital undergoes a stable complex with betacyclodextrin and complex formation would provide a better shield for the phenobarbital from hydroxyl ion attack.