Abstract: Objective: This randomized, blinded, placebo-controlled clinical trial compared the levels of interferon. (IFN-gamma), prostaglandin E-2 (PGE 2), and interleukin 6 (IL-6) in the gingival crevicular fluid (GCF) from generalized aggressive periodontitis (GAgP) patients treated with nonsurgical therapy associated or not with amoxicillin/metronidazole adjunctive. Method and Materials: Thirty-nine GAgP patients were followed during 6 months. The patients were randomly allocated to one of the groups: experimental (scaling and root planing plus 375 mg amoxicillin and 250 mg metronidazole for 7 days) and control (scaling and root planing + placebo). Probing pocket depth (PPD), relative clinical attachment level (rCAL), gingival margin position (GMP), and IL-6, IFN-gamma, and PGE 2 levels in GCF were evaluated at baseline, and at 3 and 6 months after treatment. Results: Both therapies promoted PPD reductions, rCAL gains, and recession in GMP at the end of the study, with the experimental group presenting an additional PPD reduction in full-mouth analysis and deep pockets at the 3- and 6-month follow-ups (P < .05). During the period of the study, only the experimental group promoted a reduction in PGE 2 levels in deep pockets at 3 and 6 months, while IFN-gamma and IL-6 levels remained unchanged. However, the differences in the immunologic parameters were not statistically significant among the groups. Conclusion: It can be concluded that amoxicillin/metronidazole associated with nonsurgical therapy promotes an additional PPD reduction in the treatment of GAgP; however, this therapy did not promote additional benefits in the evaluated immunologic parameters Ver menos