Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are proinflammatory cytokines that are thought to play a role in bone remodeling, bone resorption, and new bone deposition. In the present work, in situ hybridization was performed to measure the messenger RNA expression of IL-1beta, IL-6, and TNF-alpha at 3, 7, and 10 days after the application of orthodontic force on the maxillary first molars of 12 rats. The contralateral side and 3 untreated rats served as controls. Measurements of the messenger RNA expression were selected as the means to investigate the role of orthodontic force in de novo synthesis of proinflammatory cytokines. After the application of force, the induction of IL-1beta and IL-6 was observed to reach a maximum on day 3 and to decline thereafter. No messenger RNA induction of either cytokine was measured in the control teeth. The messenger RNA expression of TNF-alpha was not detected at any time point of this study in the experimental or contralateral sides or in the control animals. Our data support the hypothesis that these proinflammatory cytokines may play important roles in bone resorption after the application of orthodontic force.