Objective: This randomized, blinded, placebo-controlled clinical trial compared the levels of interferon γ (IFN-γ), prostaglandin E2 (PGE2), 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-γ, and PGE2 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 fullmouth 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 PGE2 levels in deep pockets at 3 and 6 months, while IFN-γ 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. Keywords: aggressive periodontitis, antimicrobials, interleukin-6, prostaglandin E2, interferon-γ, periodontal therapy