Outer membrane proteins (OMPs) were extracted from whole cells of several Porphyromonas and Prevotella strains and their OMPs profiles were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE analysis revealed that OMP profiles of Porphyromonas and Prevotella strains show species-specific patterns and P. gingivalis characteristically had two kinds of major outer membrane proteins (MOMPs). A 53 Kd MOMP from P. gingivalis FDC 381 and a 67 Kd MOMP from ATCC 33277 were purified. Sera from periodontitis patients and healthy subjects were analyzed for immunoreactivities against both the purified MOMPs of P. gingivalis by immunoblotting analysis. The sera from 18 patients reacted to the 53 Kd MOMP, 10 to the 67 Kd MOMP, and only three sera reacted to both MOMPs. The sera of healthy subjects also reacted, but weakly, to either the 53 Kd or 67 Kd MOMP. The SDS-PAGE OMP profiles prepared from 13 clinical isolates of P. gingivalis and immunoblotting analysis of human sera against the two kinds of P. gingivalis MOMPs indicate that periodontal diseases resulting from P. gingivalis are initiated and sustained by at least two MOMPs of P. gingivalis.