Objective: The aim of this study is to identify the nature of the IL-8 inhibitor(s) in gingival crevicular fluid (GCF). Methods: Part 1: Fourteen GCF samples were collected from 13 adult periodontitis (AP) patients, and 9 samples were taken from 8 healthy subjects. Each GCF sample was divided into two aliquots. A serine protease-specific inhibitor, PMSF, was added to one aliquot, and PBS was added to the other aliquot as control. ELISA was used to measure IL-8 level in the samples. Part 2: Forty-one GCF samples were collected from 15 AP patients and indirect ELISA was performed to detect the anti-IL-8 IgG antibody. Results: Part 1: IL-8 level in the PMSF samples was significantly greater than that in the control group (3.01 +- 5.79 mg/L vs 0.05 +- 0.15 mg/L, respectively P < .001). Part 2: The mean value of anti-IL-8 IgG in GCF was greater than that of negative control + 3 x SD. Conclusions: A serine protease that can ‘cleave’ IL-8 exists in GCF. Gingival crevicular fluid from AP sites contains an autoantibody against IL-8.