Apocynin has been extensively used as a non-toxic inhibitor of the multi-enzyme NADPH oxidase complex in phagocytic and non-phagocytic cells. Here we investigate the potency of apocynin and the related substituted methoxy-catechols, vanillic acid, methyl vanillate, 4-nitroguaiacol, 4-ethylguaiacol, 4-cyanoguaiacol and eugenol as inhibitors of NADPH oxidase of neutrophils stimulated by lipopolysaccharide (LPS) in whole blood. This experimental model was chosen as it is close to physiological conditions and could reveal the real potency of these drugs. The NADPH oxidase activation was assessed by the nitro blue tetrazolium (NBT) cytochemical assay. The drugs were pre-incubated with 300 mL whole blood and 1 mg/mL LPS for one hour at room temperature. Then, 300 mL NBT (0.1%) was added and the mixture incubated for 30 minutes at room temperature in the absence (control) or presence (0.5 mM) of methoxy-catecols. The reaction mixtures were homogenized at 10-minute intervals. The blood smears were prepared and stained with Leishman's solution. One hundred neutrophils were counted and scored as NBT-positive cells when well-defined dark spots of formazan precipitate were found in the cytoplasm. We found that besides apocynin (53% inhibition related to the control), the derivatives methyl vanillate (38%), 4-ethylguaiacol (47%) and eugenol (65%) were also efficient NADPH oxidase inhibitors. Vanillic acid (5%), 4-nitroguaiacol (1%), and 4-cyanoguaiacol (25%) were poor inhibitors.  A correlation was noted between the electron-donating and electron-withdrawing character of the substituent groups and the power to inhibit NADPH oxidase.