Although neutrophils are involved in inflammatory host defense, the overproduction of oxidant species by respiratory burst activation leads to surrounding tissue damages, at which time the pharmacological interference minimizes the deleterious consequences to host tissues. The effect of 7-epiclusianone and guttiferone-A, two natural polyisoprenylated benzophenones from Rheedia braziliensis, was investigated on the respiratory burst of inflammatory neutrophils. To clarify whether protein kinase C and tyrosine kinase participate in the action of benzophenones, the effect of specific kinase inhibitors was evaluated. Phagocytes were withdrawed from mice peritoneal inflammatory foci and superoxide anion (O₂^·-) release was determined by cytochrome c reduction. Phorbol (PMA)-induced neutrophil O₂^·- release was minimally decreased due to treatment with both benzophenones (2.5 - 200 mg/10⁷ cells; 20 min), in which staurosporine (a protein kinase C inhibitor) abolished respiratory burst, and genistein (a tyrosine kinase inhibitor) had no effect. A strong concentration-dependent inhibitory effect on the chemotatic peptide (fMLP)-induced neutrophil respiratory burst was observed in the treatment with both benzophenones, without affecting cellular viability. In addition, IC₅₀ (concentration necessary to inhibit 50% of O₂^·- release) was determined. 7-epiclusianone supressed O₂^·- release by neutrophils with an IC₅₀=20 mg/10⁷ cells (p<0.01), while gutifferone-A exhibited an IC₅₀=12 mg/10⁷ cells (p<0.001). In these conditions, a weak action of staurosporine on the neutrophil respiratory burst was observed, while the inhibitory effect of benzophenones was exacerbated by genistein. These results suggest that both 7-eppiclusianone and guttiferone-A are able to downregulate the respiratory burst of inflammatory neutrophils trough a participation of tyrosine kinase in the biochemical pathway. Furthermore, the higher efficacy of guttiferone-A as compared to that of 7-epiclusianone can be ascribed to the presence of hydroxyl groups in the chemical structure of the former compound, contrasting with the absence of hydroxyl groups in 7-epiclusianone.