In the present study we measured the inhibition by 34 compounds, either flavonoids or related substances, of the release of reactive oxygen species by human neutrophils after stimulation by three agents: the bacterial peptide N-fMetLeuPhe (FMLP), the protein kinase C activator phorbol myristate acetate (PMA) or opsonized zymosan (OZ), using two chemiluminescent probes, lucigenin or luminol in the presence or absence of horseradish peroxidase (HRP). The data matrix (34 x 7) was submitted to multivariate analysis: first, a correspondence factorial analysis to uncover levels of correlation among the biochemical parameters and the specificity of action of the test-compounds and second, a minimum spanning tree analysis that classified the chemical structures into a network describing both specificity and amplitude of the inhibition of the chemiluminescence response. The major conclusions of the analyses were: (a) opposition between inhibition of poly-morphonuclear leukocytes (PMNs) stimulated by FMLP and of PMNs stimulated by PMA or OZ implying that, for the molecules under study, there was a fundamental difference in the manner in which this inhibition occurred and, conversely, a difference in the nature of the stimulatory action of these activators. Molecules lacking hydroxyl groups on ring B, i.e. chrysin, chalcone, flavone and galangin, molecules glycosylated in position 7, i.e. hesperidin and naringin and ring B mono-hydroxylated molecules were, for the most part, at the origin of this dichotomy and might interfere with the membrane FMLP receptor; (b) a marked difference in chemiluminescence inhibition in the presence or absence of HRP that can be explained by the differential action of catechins compared to flavone and flavonol derivatives; (c) a similarity in biological profile between non-flavonoids such as chalcone and phloretin and low mean-activity flavonoids such as chrysin and galangin and between the non-flavonoid curcumin and the highly active flavonoid isorhamnetin; (d) a reaffirmation of the importance of ring A (C5,7) and ring B (C3',4') dihydroxylation, ring C (C3) hydroxylation, but also of the presence of a methoxy group on ring B in engendering high potency. This potency is generally decreased by C2-C3 saturation and by glycosylation. The most active molecules identified in this study provide valuable information for the selection of simpler molecules (e.g. metabolites accounting for the potency of orally administered flavonoids) for further structure-activity relationship (SAR) studies that could lead to the design of novel drugs or prodrugs.