We have previously demonstrated that Porphyromonas gingivalis is susceptible to killing by toluidine blue O (TBO) when irradiated with light from a helium-neon (HeNe) laser. The aim of this study was to determine whether a TBO-antibody conjugate (Ab-TBO) could be used to specifically target P. gingivalis to lethal photosensitization in the presence of Streptococcus sanguis or human gingival fibroblasts (HGFs). When a mixture of P. gingivalis and S. sanguis was exposed to 4 µg of TBO/ml and irradiated with HeNe laser light, there were 1.5- and 4.0-log₁₀-unit reductions in the viable counts, respectively. In contrast, when TBO was conjugated with a murine monoclonal antibody against P. gingivalis lipopolysaccharide, the reductions in viable counts of P. gingivalis and S. sanguis amounted to 5.0 and 0.1 log₁₀ units, respectively. Lethal photosensitization of P. gingivalis in the presence of HGFs using unconjugated TBO resulted in a 0.7-log₁₀-unit reduction in P. gingivalis viable counts and a 99% reduction in the incorporation of tritiated thymidine ([³H]Tdr) by the HGFs. In contrast, when the Ab-TBO conjugate was used, there was a 100% reduction in P. gingivalis viable counts but no significant reduction in the incorporation of [³H]Tdr by HGFs. These results demonstrate that specific targeting of P. gingivalis can be achieved using TBO conjugated to a monoclonal antibody raised against a cell surface component of this organism.