BACKGROUND: Peri-implantitis is an inflammatory process caused by microorganisms affecting the tissues around an osseointegrated implant in function, resulting in a loss of supporting bone. Limited data exist regarding the treatment of peri-implantitis. The aim of this study was to assess the clinical and microbiologic outcome of repeated local administration of minocycline microspheres, 1 mg, in cases of peri-implantitis. METHODS: Thirty-two subjects with at least one implant with a probing depth > or =4 mm combined with bleeding and/or exudate on probing and the presence of putative pathogenic bacteria were included in the study. At baseline, subjects were randomly assigned to receive local minocycline microspheres (17 subjects and 57 implants) or chlorhexidine gel (15 subjects and 38 implants) following debridement. Treatments were performed on three occasions: baseline and days 30 and 90. Follow-up examinations were conducted at 10 days and at 1, 3, 6, 9, and 12 months. RESULTS: The use of minocycline resulted in significant improvements in probing depths compared to chlorhexidine at days 30, 90, and 180 (P = 0.5, P = 0.01, and P = 0.04, respectively). For the deepest sites of the minocycline-treated implants, the mean probing depth reduction was 0.6 mm at 12 months. Regarding bleeding on probing, significant differences between groups, based on all four sites at the implants, were found at days 30, 90, 180, 270, and 360. Both treatments resulted in a marked reduction in the indicator bacteria. CONCLUSIONS: The use of a repeated local antibiotic as an adjunct to the mechanical treatment of peri-implantitis lesions demonstrated improvements in probing depths that were significantly different from controls and were sustained for 6 months. The adjunctive use of minocycline microspheres is beneficial in the treatment of peri-implant lesions, but the treatment may have to be repeated.