Background: Prevalence of Grade C molar incisor periodontitis (C/MIP) in females (F) and males (M) is controversial, although some studies suggest higher prevalence in females. The objective of this study was to evaluate differences in clinical parameters, and levels of cyto/chemokines in gingival crevicular fluid (GCF) and peripheral blood response. Methods: GCF and blood were collected from 79 C/MIP African-American participants (53F and 26 M) and healthy controls (58F and 38 M), aged 5 to 23. Blood was stimulated with ultrapure LPS from Escherichia coli (Ec) and Porphyromonas gingivalis (Pg) and we quantified levels of 14 cyto/chemokines. Clinical parameters were collected before and 12 months following treatment Results: No clinical parameters or age differences were found between males and females, although age was negatively correlated with response to treatment. GCF levels of TNFα, IFNγ, MIP1α, and MCP1 from diseased and sites and healthy sites IFNγ levels were higher in M (P < 0.05). C/MIP females presented higher Pg and Ec LPS induced levels of Eotaxin, IFNγ, and GMCSF (P < 0.05), whereas healthy males presented higher Ec LPS induced levels of Eotaxin and IFNγ (P < 0.05). Inflammatory profiles were also different among genders in disease (P = 0.004).