Host susceptibility to periodontal infection is controlled by genetic factors. As a step toward identifying and cloning these factors, we generated an A/J x BALB/cJ F2 mouse resource population. A genome-wide search for Quantitative Trait Loci (QTL) associated with periodontitis was performed. We aimed to quantify the phenotypic response of the progenies to periodontitis by microCT analysis, to perform a genome-wide search for QTL associated with periodontitis, and, finally, to suggest candidate genes for periodontitis. We were able to produce 408 F2 mice. All mice were co-infected with Porphyromonas gingivalis and Fusobacterium nucleatum bacteria. Six weeks following infection, alveolar bone loss was quantified by computerized tomography (microCT) technology. We found normal distribution of the phenotype, with 2 highly significant QTL on chromosomes 5 and 3. A third significant QTL was found on chromosome 1. Candidate genes were suggested, such as Toll-like receptors (TLR) 1 and 6, chemokines, and bone-remodeling genes (enamelin, ameloblastin, and amelotin). This report shows that periodontitis in mice is a polygenic trait with highly significant mapped QTL.