Treponema denticola, a suspected periodontal pathogen, was shown to agglutinate and lyse human red blood cells. Both activities were cell-associated, heat-labile, and produced during the exponential growth phase. Hemolytic activity was time-dependent and required incubation at 37 degrees C; further incubation at 4 degrees C increased the hemolysis. Hemagglutination was reduced in the presence of D-glucosamine, EDTA or sodium salicylate, whereas hemolytic activity was affected by calcium chloride, magnesium chloride, EDTA or sodium salicylate. These biological activities may favor a higher concentration of hemin-containing compounds in periodontal sites, and therefore represent additional potential virulence mechanisms.