The purpose of this study was to evaluate the effects of a light continuous force and an interrupted force with weekly reactivation on interleukin-1beta (IL-1beta) and prostaglandin E(2) (PGE(2)); possible interactions between these 2 potent mediators of the bone resorption process were assessed in vivo. Ten healthy young adults (mean age 20.6 years, 2 men, 8 women) with 4 premolars extracted were assessed. In each subject, 1 maxillary canine (E1) received continuous force with a nickel-titanium coil spring. The opposite canine (E2) received an interrupted force with a screw-attached retractor; the force was reactivated weekly by 2 turns of the screw. An antagonistic canine was used as a control. Gingival crevicular fluid was collected from the distal side of each tooth, 10 times in 3 weeks, and IL-1beta and PGE(2) levels were measured. For E1, the IL-1beta level showed a significant elevation at 24 hours and then decreased and maintained an insignificant but high mean concentration, compared with the control site. The PGE(2) level showed a significant elevation at 24 hours and then decreased. For E2, a significant elevation of IL-1beta level was observed at 24 hours and a greater significant elevation at 24 hours after the first reactivation, compared with the control sites. The PGE(2) level increased significantly at 24 hours and remained high for 1 week. The synergistic up-regulation of PGE(2) by appliance reactivation and secreted IL-1beta was not evident with either type of force after 1 week. Both experimental sites showed significant tooth movement compared with the control sites at 3 weeks; however, there was no significant difference between the 2 experimental sites. A well-controlled mechanical stress with timely reactivation can effectively upregulate IL-1beta secretion, but there might be limitations in increasing the mediator levels, because of the feedback mechanisms in vivo. In addition, the analysis of crevicular fluid is a useful method for assessing cellular response to orthodontic force in vivo.