Objective: To monitor the effects of rapid maxillary expansion (RME) on bone metabolic activities during and after 3 months of retention. Study Design: Fifteen patients with a mean age of 12.9 +/- 0.6 years were treated with a bonded expansion device, activated 2 turns per day. The retention period was 3 months. Clinical periodontal parameters were recorded at baseline and after retention. Gingival crevicular fluid (GCF) samples were collected from maxillary first molars from the compression sides at baseline, then at 1 and 10 days and after retention. Tension side samples were obtained at baseline and after retention. Interleukin-1beta (IL-1 beta), transforming growth factor betal (TGF-beta 1), prostaglandin E-2 (PGE(2)) and nitric oxide (NO) levels were specifically measured. Results: Periodontal parameters increased significantly after retention relative to baseline values. Levels of IL-1 beta, TGF-beta 1 and PGE(2) increased on day 10, and decreased after retention on the compression side. NO levels were elevated on day 10, and remained higher after retention on the compression side. Tension side cytokine levels remained higher relative to baseline values after retention. Conclusions: The results of this study indicate the importance of ongoing adaptive bone activities after 3 months of retention with RME, which should be considered questionable as an effective retention period.