Decreased neutrophil chemotaxis has been implicated in the pathophysiology of the disease, localized juvenile periodontitis (LJP). The biological basis for the altered neutrophil function in LJP has been suggested to be an intrinsic cellular defect, involving a decrease in the number of N-formyl-methionyl-leucyl-phenylalanine (FMLP) receptors on the cell surface. We have investigated the relative contribution of serum-borne factors in the modulation of neutrophil functions in LJP, in a large population of LJP patients and healthy control subjects (HS). Treatment of HS-neutrophils with LJP-sera, resulted in a decreased neutrophil chemotactic response, and down regulation of FMLP receptors on the cell surface. Pretreatment of LJP-sera with anti-TNF and anti-IL-1 antibodies effectively, although incompletely, neutralized the ability of LJP-sera to modulate chemotaxis and FMLP receptor levels in HS-neutrophils. The changes induced by LJP sera were specific and sustained and could not be reversed by placing LJP-serum treated neutrophils in HS-serum. Sera obtained from HS and patients with adult periodontitis (AP), both of which exhibit normal chemotaxis, and patients with clinically diagnosed LJP with normal neutrophil chemotaxis (LJP-nctx) did not modulate HS neutrophil chemotaxis or FMLP receptors. Furthermore, recombinant human TNF-alpha, rhIL-1 alpha and rhIL-1 beta, at very low concentrations (15 pg/ml to 150 pg/ml), modulated the chemotactic response as well as FMLP receptor numbers on HS-neutrophils, in a manner similar to those observed in LJP. The present findings demonstrate that the biologic basis for the altered neutrophil function may not be an intrinsic cellular defect in neutrophils, but at least in part due to quantitatively small but biologically significant elevations in the levels of TNF-alpha and IL-1 in the serum.