Periodontal pathogenic bacteria are associated with elevated levels of interleukin-1α (IL-1α) but it is unclear if all species can induce cytokine production equally. Porphyromonas gingivalis may be able antagonize IL-1α induced by other species through the activity of its proteases or lipopolysaccharide (LPS). Monomac-6 cells and primary human monocytes were treated with culture supernatants from Porphyromonas gingivalis, Fusobacterium nucleatum, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedius, Veillonella atypical and Prevotella nigrescens. IL-1α protein levels were measured after 6 h of incubation. In addition, monocytes were co-stimulated with supernatants from P. gingivalis and other bacteria. The role of P. gingivalis proteases was tested using Arg-X and Lys-X mutant strains. The role of LPS was investigated using purified P. gingivalis LPS and polymixin depletion. All species tested induced significant IL-1α production, but P. gingivalis was the weakest. Co-stimulation of monocytes with P. gingivalis antagonized the ability of other bacterial species to induce IL-1α production. This effect was at its greatest with C. rectus (resulting in a 70% reduction). Gingipain mutant strains and chemical inhibition of protease activity did not reduce antagonistic activity. However, 100 ng/ml of P. gingivalis LPS can reproduce the antagonistic activity of P. gingivalis culture supernatants. Periodontitis-associated bacterial species stimulate IL-1α production by monocytes. P. gingivalis can antagonize this effect, and its LPS appears to be the crucial component. This study highlights the importance of mixed infections in the pathogenesis of periodontal disease because reduction of pro-inflammatory cytokine levels may impair the ability of the host to tackle infection.