The inhibition of superoxide (O2-) production by human peripheral blood polymorphonuclear leukocytes (PMNs) in the presence of oral treponemes, their cellular components, and their culture supernatants was investigated. Superoxide production was inhibited 56% by a 25-microgram/ml phenol extract of a human clinical isolate. Inhibition by culture supernatants of both the clinical isolate and a reference strain was related to the bacterial phase of growth and viability, though inhibition also persisted in the decline phase. Inhibition of superoxide production was not evident when either opsonized or nonopsonized whole spirochetes were reacted with PMNs. The suppressive activity depended, therefore, on the treponemes either being disrupted or growing and releasing the inhibitory factor into the culture medium. These results suggest that oral treponemes possess factors which interfere with the activity of PMNs and thereby alter the inflammatory process in the diseased periodontal pocket.