Accumulating evidence indicates that epithelia are not merely mechanical barriers but also important elements of the innate immune system. The present study was performed to examine cytokine responses of oral epithelial cells after infection with the periodontal pathogen Porphyromonas gingivalis. The KB-cell line and primary cultures of periodontal pocket epithelium were infected with P. gingivalis for assessment of bacterial invasion by an antibiotic protection assay, and examination of expression of interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha by in situ hybridization and immunohistochemistry. We observed that P. gingivalis induces a strong cytokine response, positively correlated with the adhesive/invasive potential of the infecting strain, in both KB cells and primary cultures. These findings indicate that the epithelial cells of the periodontal pocket are an integral part of the immune system, eliciting cytokine responses to a bacterial challenge. In this context, the adhesive/invasive phenotype of P. gingivalis appears to contribute to pathogenicity.