Porphyromonas gingivalis has been implicated as a major pathogen in periodontitis. To determine the role of T cells in the regulation of this disease, a method was developed for the generation and characterization of rat T-cell clones with antigen specificity to P. gingivalis whole cells. The clones studied so far demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8− and OX22−. These T-cell clones proliferated in vitro in response to P. gingivalis, but not to other bacteria ( Prevotella intermedia, Actinobacillus actinomycetemcomitans, Wolinella recta, Fusobacterium nucleatum, Streptococcus sanguis). Limiting dilution analysis showed W3/25+, OX8− T cells preferentially respond to P. gingivalis, rather than W3/25−, OX8+ T cells. P. gingivalis-reactive W3/25+ T cells belonged to the OX22− population, suggesting that the OX22− T cells may represent memory cells. All clones tested produced interferon γ, but not interleukin 2. The cloned T-cell F1 significantly enhanced P. gingivalis-specific antibody production ( p < 0.03). The availability of these cloned T cells should bring new insight into the mechanism by which T cells regulate oral health and periodontal disease.